Intra-arterial therapy (IAT) has been used for three decades to promote recanalisation after stroke. Whereas results of the Prolyse in Acute Cerebral Thromboembolism-II trial (PROACT-II) showed significant improvement in clinical outcome with intraarterial fibrinolysis, the stroke specialty received some disturbing news in 2013. Results of the Interventional Management of Stroke-III (IMS-III), SYNTHESIS, and Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) studies failed to show an increased benefit for IAT compared with intravenous alteplase (t-PA) or as an adjunctive approach to intravenous alteplase. [reference: Stroke roundup 2013. Lancet neurology, 2014]
The above description is for all IAT, not only for IAT of BA occlusion.
Although we continue to achieve high reperfusion rates with IAT, these successful radiographical outcomes do not always translate to good clinical outcomes. This gap raises the important issue of patient selection for IAT.
My comment: clinical outcome is the most important. Therefore, the important thing is whether and when the thrombolytic therapy should be done. As to the way of thrombolysis, IAT or IVT, I prefer IVT. Recognition of mode of onset is one of the important factors in making decision of intervention to treat BAO.
For those patients with high risk, prolonged low dose IVT may be a new treatment. This deserves further observation. [As to the issue about “Prolonged Low-Dose Thrombolysis in Posterior Circulation Stroke”, reference is Neurocrit Care. 2013 Nov 19. (Epub ahead of print)].
2014年1月3日 星期五
2013年11月4日 星期一
側記 Brodmann
Brodmann’s map是由德國內科醫師Krobinian Brodmann在1903至1908年間提出，有52區。
常謂塞翁失馬，焉知非福，在Brodmann身上，又是一例。Brodmann在他通過考試之後，原本是想從事臨床工作，然而卻不幸染上白喉，於是只得找一個比較輕鬆點的工作。所以他到Oskar Vogt的研究室，當一名研究助理；那時候是1896年5月，是他一生中的關鍵時刻：Vogt 當時正在籌建的Institute of Brain Research，十分吸引Brodmann，使得Brodmann再短暫追隨Vogt之後，又去Leipzig學pathology。在那裡，他拿到了醫學博士學位；然後，他再到Frankfurt 的University Psychiatric Clinic，接受Otto Binswanger的指導。從1900至1901年間，他在Frankfurt共待了18個月，當時在Frankfurt有一群既傑出又有衝勁的神經解剖學家，Brodmann身處其間，似飲曹溪一滴水，受益匪淺。Brodmann也是在那時候，遇上了Alois Alzheimer。Alzheimer 從1882年到1902年一直待在Frankfurt，當時他和Nissl密切合作，仔細地觀察大腦皮質之組織病理(histopathology)。
在1901年的秋天，Brodmann又回到Oskar Vogt在Berlin新成立的研究室。在那裡，他又遇到了Max Bielschowsky這位很會染神經纖維的大師。從1901年到1910年，就在Vogt的實驗室裡，Bielschowsy與Brodmann分工合作：Bielschowsy所負責的fibrilloarchitectonics及myelinoarchitectonics (based on the onset of myelination in different brain regions) 是Oskar Vogt的最大興趣，而Brodmann則負責cytoarchitectonics的研究。自1903年至1908年陸續發表很多papers來描述fine structure of cerebral cortex in a number of mammals (特別是primates)，而在1909年發表鉅著Vergleichende Lokalisationslehre der Grosshirnrinde [Localization in the cerebral hemisphere: a comprehensive study]。雖然Brodmann並不是史上唯一研究cytoarchitectonics的人，然而他提出的map，特別是他賦予每個區域的編號，卻是永垂青史。
精誠所至，金石為開。能做出這樣的事業，必有相當堅定的信念在他心裡。Brodmann想要為人所不敢為。當時的神經學者，腦中有個古怪的念頭，認為人的腦子既然負責一些心理及行為上的功能，那麼在腦子裡就應存有〝memory〞cell或〝psychi〞cell。但是Brodmann並不這麼認為。他認為這些心理或行為上的表現，並非僅憑單一細胞，而得靠一群細胞(cell grouping)才能達成這些表現。所以在他的腦子哩，有這麼兩種假說：
第一、物以類聚：意即，相似的細胞會聚在一起；
第二、細胞結構簡單者，其功能就簡單，不會複雜。
Brodmann服膺Bernhard Gudden所言，認為若想要研究function localization，必先研究出anatomy的具象事實，藉此才能衍生physiology的抽象觀念；若是先有physiology的理論，缺乏anatomy基礎，那麼一切可能流於虛妄空談。且不論他所想的兩種假說是否正確，不過以上的信念迄今仍被傳頌。
常謂塞翁失馬，焉知非福，在Brodmann身上，又是一例。Brodmann在他通過考試之後，原本是想從事臨床工作，然而卻不幸染上白喉，於是只得找一個比較輕鬆點的工作。所以他到Oskar Vogt的研究室，當一名研究助理；那時候是1896年5月，是他一生中的關鍵時刻：Vogt 當時正在籌建的Institute of Brain Research，十分吸引Brodmann，使得Brodmann再短暫追隨Vogt之後，又去Leipzig學pathology。在那裡，他拿到了醫學博士學位；然後，他再到Frankfurt 的University Psychiatric Clinic，接受Otto Binswanger的指導。從1900至1901年間，他在Frankfurt共待了18個月，當時在Frankfurt有一群既傑出又有衝勁的神經解剖學家，Brodmann身處其間，似飲曹溪一滴水，受益匪淺。Brodmann也是在那時候，遇上了Alois Alzheimer。Alzheimer 從1882年到1902年一直待在Frankfurt，當時他和Nissl密切合作，仔細地觀察大腦皮質之組織病理(histopathology)。
在1901年的秋天，Brodmann又回到Oskar Vogt在Berlin新成立的研究室。在那裡，他又遇到了Max Bielschowsky這位很會染神經纖維的大師。從1901年到1910年，就在Vogt的實驗室裡，Bielschowsy與Brodmann分工合作：Bielschowsy所負責的fibrilloarchitectonics及myelinoarchitectonics (based on the onset of myelination in different brain regions) 是Oskar Vogt的最大興趣，而Brodmann則負責cytoarchitectonics的研究。自1903年至1908年陸續發表很多papers來描述fine structure of cerebral cortex in a number of mammals (特別是primates)，而在1909年發表鉅著Vergleichende Lokalisationslehre der Grosshirnrinde [Localization in the cerebral hemisphere: a comprehensive study]。雖然Brodmann並不是史上唯一研究cytoarchitectonics的人，然而他提出的map，特別是他賦予每個區域的編號，卻是永垂青史。
精誠所至，金石為開。能做出這樣的事業，必有相當堅定的信念在他心裡。Brodmann想要為人所不敢為。當時的神經學者，腦中有個古怪的念頭，認為人的腦子既然負責一些心理及行為上的功能，那麼在腦子裡就應存有〝memory〞cell或〝psychi〞cell。但是Brodmann並不這麼認為。他認為這些心理或行為上的表現，並非僅憑單一細胞，而得靠一群細胞(cell grouping)才能達成這些表現。所以在他的腦子哩，有這麼兩種假說：
第一、物以類聚：意即，相似的細胞會聚在一起；
第二、細胞結構簡單者，其功能就簡單，不會複雜。
Brodmann服膺Bernhard Gudden所言，認為若想要研究function localization，必先研究出anatomy的具象事實，藉此才能衍生physiology的抽象觀念；若是先有physiology的理論，缺乏anatomy基礎，那麼一切可能流於虛妄空談。且不論他所想的兩種假說是否正確，不過以上的信念迄今仍被傳頌。
2013年5月11日 星期六
Buerger’s disease and cigarette filter
Adapted from Wikipedia
Buerger's disease was first reported by Felix von Winiwarter in 1879 in Austria. It wasn't until 1908 that the disease was given its first accurate pathological description, by Leo Buerger at Mount Sinai Hospital in New York City. Buerger called it "presenile spontaneous gangrene" after studying amputations in 11 patients.
It is strongly associated with use of tobacco products, primarily from smoking.
As to the structure of cigarette at that time, tobacco was simply wrapped by a piece of paper.
In 1925, inventor Boris Aivaz patented the process of making a cigarette filter from crepe paper. Aivaz produced the first cigarette filter from 1927, but uptake was low due to a lack of the machinery required to produce cigarettes with the filtered tip.
From 1935, a British company began to develop a machine that made cigarettes incorporating the tipped filter. Since filtered cigarettes were considered "safer", by the 1960s, they dominated the market.
Buerger's disease was first reported by Felix von Winiwarter in 1879 in Austria. It wasn't until 1908 that the disease was given its first accurate pathological description, by Leo Buerger at Mount Sinai Hospital in New York City. Buerger called it "presenile spontaneous gangrene" after studying amputations in 11 patients.
It is strongly associated with use of tobacco products, primarily from smoking.
As to the structure of cigarette at that time, tobacco was simply wrapped by a piece of paper.
In 1925, inventor Boris Aivaz patented the process of making a cigarette filter from crepe paper. Aivaz produced the first cigarette filter from 1927, but uptake was low due to a lack of the machinery required to produce cigarettes with the filtered tip.
From 1935, a British company began to develop a machine that made cigarettes incorporating the tipped filter. Since filtered cigarettes were considered "safer", by the 1960s, they dominated the market.
2013年2月16日 星期六
Reticular Reflex Myoclonus
The following sections about reticular reflex myoclonus was excerpted from Eplilesy textbook on 2013/02/16
Reticular reflex myoclonus originates in a hyperexcitable caudal brainstem reticular formation, giving rise to a widespread pattern of muscle activation with proximal and flexor predominance, spontaneous or induced by various stimuli. The impulses may travel up the brainstem. Reticular reflex myoclonus may be present simultaneously with cortical myoclonus.
Reticular reflex myoclonus is not time-locked to EEG discharges, and the sensory evoked potentials are not enhanced. Myoclonus is triggered by stimuli, but the temporal relationship is variable between the stimuli and the myoclonus, whereas it is constant in patients with cortical reflex myoclonus. The EMG discharges start in the areas of lower cranial nerves (sternocleidomastoid muscle, trapezius muscle). They go up to the facial muscles, down to the upper limbs, then to lower limbs. Therefore, it was speculated that the stimuli excited the reticular formation and that abnormal electrical activity then spread from it to the upper brainstem and the spinal cord.
Reticular reflex myoclonus originates in a hyperexcitable caudal brainstem reticular formation, giving rise to a widespread pattern of muscle activation with proximal and flexor predominance, spontaneous or induced by various stimuli. The impulses may travel up the brainstem. Reticular reflex myoclonus may be present simultaneously with cortical myoclonus.
Reticular reflex myoclonus is not time-locked to EEG discharges, and the sensory evoked potentials are not enhanced. Myoclonus is triggered by stimuli, but the temporal relationship is variable between the stimuli and the myoclonus, whereas it is constant in patients with cortical reflex myoclonus. The EMG discharges start in the areas of lower cranial nerves (sternocleidomastoid muscle, trapezius muscle). They go up to the facial muscles, down to the upper limbs, then to lower limbs. Therefore, it was speculated that the stimuli excited the reticular formation and that abnormal electrical activity then spread from it to the upper brainstem and the spinal cord.
Thalamocortical myoclonus
The following sections about thalamocortical myoclonus was excerpted from Eplilesy textbook on 2013/02/16
Thalamocortical myoclonus or idiopathic generalized epileptic myoclonus represents the common type of myoclonus in various epileptic syndromes. Myoclonia are often spontaneous, predominantly arrhythmic and axial with varying severity, and associated chronologically with an EEG pattern of diffuse polyspikes or (poly) spike-and-wave discharges. A hyperexcitable cortex is thought to be driven diffusely and synchronously by ascending subcortical inputs that trigger the paroxysmal events. As a consequence, muscles from both sides are activated, and muscles innervated by the cranial nerves are involved through a rostrocaudal manner.
Electrophysiologically, SEP usually does not show giant SEP, and C-reflex may be recorded at rest. A negative peak of the generalized spike (30–100 msec duration) precedes the jerk (<100 msec duration) by 20 to 75 msec. The latency of the spike is relatively longer, and the temporal relationship is looser than in that of cortical myoclonus. The underlying mechanism of the thalamocortical myoclonus is still uncertain. The myoclonus of benign myoclonic epilepsy of infancy, myoclonic-astatic epilepsy, and JME belongs to this category.
Myoclonus observed in patients with Dravet syndrome is not straightforward: Patients may exhibit massive myoclonus combined with a generalized spike-wave (rarely in infancy, mostly in childhood), and erratic myoclonus, particularly during episodes of myoclonic status, in which the patient is drowsy with diffuse slow wave activity and few spikes. The generator remains unidentified.
Thalamocortical myoclonus or idiopathic generalized epileptic myoclonus represents the common type of myoclonus in various epileptic syndromes. Myoclonia are often spontaneous, predominantly arrhythmic and axial with varying severity, and associated chronologically with an EEG pattern of diffuse polyspikes or (poly) spike-and-wave discharges. A hyperexcitable cortex is thought to be driven diffusely and synchronously by ascending subcortical inputs that trigger the paroxysmal events. As a consequence, muscles from both sides are activated, and muscles innervated by the cranial nerves are involved through a rostrocaudal manner.
Electrophysiologically, SEP usually does not show giant SEP, and C-reflex may be recorded at rest. A negative peak of the generalized spike (30–100 msec duration) precedes the jerk (<100 msec duration) by 20 to 75 msec. The latency of the spike is relatively longer, and the temporal relationship is looser than in that of cortical myoclonus. The underlying mechanism of the thalamocortical myoclonus is still uncertain. The myoclonus of benign myoclonic epilepsy of infancy, myoclonic-astatic epilepsy, and JME belongs to this category.
Myoclonus observed in patients with Dravet syndrome is not straightforward: Patients may exhibit massive myoclonus combined with a generalized spike-wave (rarely in infancy, mostly in childhood), and erratic myoclonus, particularly during episodes of myoclonic status, in which the patient is drowsy with diffuse slow wave activity and few spikes. The generator remains unidentified.
Cortical myoclonus
The following sections about cortical myoclonus was excerpted from Eplilesy textbook on 2013/02/16
Cortical myoclonus reflects impulses that originate in the sensorimotor cortex and travel down the brainstem. Cortical myoclonus is typically seen in progressive myoclonus epilepsy. Muscles involved tend to be distal more than proximal and flexor more than extensor, and to involve more the face and upper extremities than the rest of the body. Cortical myoclonus is more commonly encountered in a multifocal form, presenting with multifocal spike discharges. If myoclonus is triggered by stimuli, the term cortical reflex myoclonus is used. If myoclonus occurs periodically, the term epilepsia partialis continua is used. The neurons in the sensorimotor cortex may be primarily hyperexcitable, or may be driven by abnormal inputs from the neurons of other brain parts. Therefore, cortical myoclonus occasionally is called fragmented epileptic convulsion.
In patients with cortical reflex myoclonus, the cortical components of median-nerve SEP showed abnormally large amplitude. Usually, the initial peaks (N20/P22) are not large, and the following components become higher. This giant SEP is thought to indicate hyperexcitability of the sensorimotor cortex. Abnormally large evoked potentials were also reported by photic stimulation.
When the peripheral nerve is stimulated, the stimulus goes up the spino-thalamo-cortical tract and, after excitation of the pyramidal neuron, it goes down the cortico-spinal tract, resulting in muscle contraction (long-loop reflex). In normal subjects, long-loop reflex can be recorded only when subjects maintain muscle contractions. In patients with cortical reflex myoclonus, however, this reflex can be recorded even while resting (C-reflex). The latency of C-reflex for median nerve stimulation is about 40 to 45 msec, which is almost double of the latency of N20 to the median nerve stimulation. When the C-reflex is recorded from the contralateral limbs to the stimuli, the latency delay is about 10 msec to the ipsilateral limbs, which corresponds to the traveling time of the transcallosal pathway. This stimulation-locked muscle contraction is believed to share the same underlying mechanism with cortical reflex myoclonus.
Some EEG correlates are time-locked to cortical myoclonus. However, because of the relatively smaller amplitude of the EEG spikes in comparison with the background activities, the physiologic correlates of myoclonus can only be detected by using jerk-locked (EEG or magnetoencephalograhic [MEG]) averaging (JLA of jerk-locked magentic field [JLF]) or coherence analysis method. In JLA, EEGs are averaged with respect to the EMG onset, to reduce the non–time locked background EEG activities. Positive peak of the EEG spikes is 15 to 20 msec prior to the myoclonus for the upper limbs, and 25 to 40 msec for the lower limbs. Spikes are located around the contralateral primary motor cortex.
As such, cortical reflex myoclonus is caused by hyperexcitability of the primary sensorimotor cortex. However, because giant SEPs are not always present in patients with cortical reflex myoclonus (as in dentatorubral-pallidoluysian atrophy [DRPLA]), some other pathophysiologic mechanisms may exist.
In Lennox-Gastaut syndrome (LGS), myoclonus is rare and disclosed only in those cases with a cortical lesion affecting the rolandic area; thus, myoclonus appears to be produced by a secondary generalization of focal cortical myoclonus. They also present with arrhythmic, distal small focal jerks, leading to the individual tiny finger movements unaccompanied by premyoclonic potentials on JLA that Wilkins et al. proposed to call minipolymyoclonus. Brown et al. indicated that the major role of facilitation of inter- and intra-hemispheric spread of cortical myoclonic activity is through trans-callosal or intrahemispheric corticocortical pathways in producing generalized or bilateral myoclonus. Therefore, bilateral jerks may not be synchronous in patients with cortical myoclonus.
Cortical myoclonus reflects impulses that originate in the sensorimotor cortex and travel down the brainstem. Cortical myoclonus is typically seen in progressive myoclonus epilepsy. Muscles involved tend to be distal more than proximal and flexor more than extensor, and to involve more the face and upper extremities than the rest of the body. Cortical myoclonus is more commonly encountered in a multifocal form, presenting with multifocal spike discharges. If myoclonus is triggered by stimuli, the term cortical reflex myoclonus is used. If myoclonus occurs periodically, the term epilepsia partialis continua is used. The neurons in the sensorimotor cortex may be primarily hyperexcitable, or may be driven by abnormal inputs from the neurons of other brain parts. Therefore, cortical myoclonus occasionally is called fragmented epileptic convulsion.
In patients with cortical reflex myoclonus, the cortical components of median-nerve SEP showed abnormally large amplitude. Usually, the initial peaks (N20/P22) are not large, and the following components become higher. This giant SEP is thought to indicate hyperexcitability of the sensorimotor cortex. Abnormally large evoked potentials were also reported by photic stimulation.
When the peripheral nerve is stimulated, the stimulus goes up the spino-thalamo-cortical tract and, after excitation of the pyramidal neuron, it goes down the cortico-spinal tract, resulting in muscle contraction (long-loop reflex). In normal subjects, long-loop reflex can be recorded only when subjects maintain muscle contractions. In patients with cortical reflex myoclonus, however, this reflex can be recorded even while resting (C-reflex). The latency of C-reflex for median nerve stimulation is about 40 to 45 msec, which is almost double of the latency of N20 to the median nerve stimulation. When the C-reflex is recorded from the contralateral limbs to the stimuli, the latency delay is about 10 msec to the ipsilateral limbs, which corresponds to the traveling time of the transcallosal pathway. This stimulation-locked muscle contraction is believed to share the same underlying mechanism with cortical reflex myoclonus.
Some EEG correlates are time-locked to cortical myoclonus. However, because of the relatively smaller amplitude of the EEG spikes in comparison with the background activities, the physiologic correlates of myoclonus can only be detected by using jerk-locked (EEG or magnetoencephalograhic [MEG]) averaging (JLA of jerk-locked magentic field [JLF]) or coherence analysis method. In JLA, EEGs are averaged with respect to the EMG onset, to reduce the non–time locked background EEG activities. Positive peak of the EEG spikes is 15 to 20 msec prior to the myoclonus for the upper limbs, and 25 to 40 msec for the lower limbs. Spikes are located around the contralateral primary motor cortex.
As such, cortical reflex myoclonus is caused by hyperexcitability of the primary sensorimotor cortex. However, because giant SEPs are not always present in patients with cortical reflex myoclonus (as in dentatorubral-pallidoluysian atrophy [DRPLA]), some other pathophysiologic mechanisms may exist.
In Lennox-Gastaut syndrome (LGS), myoclonus is rare and disclosed only in those cases with a cortical lesion affecting the rolandic area; thus, myoclonus appears to be produced by a secondary generalization of focal cortical myoclonus. They also present with arrhythmic, distal small focal jerks, leading to the individual tiny finger movements unaccompanied by premyoclonic potentials on JLA that Wilkins et al. proposed to call minipolymyoclonus. Brown et al. indicated that the major role of facilitation of inter- and intra-hemispheric spread of cortical myoclonic activity is through trans-callosal or intrahemispheric corticocortical pathways in producing generalized or bilateral myoclonus. Therefore, bilateral jerks may not be synchronous in patients with cortical myoclonus.
Stereotypies
The following paragraph was taken from textbook "Neurology and clinical neuroscience" on 2013/02/05:
Stereotypies are repetitive, rhythmical, and invariant motor behaviors, without an apparent purpose or function, that can vary from simple motor behaviors such as rocking or hand waving to extraordinarily complex acts and rituals. They are one of the defining features of autism and are common in patients with mental retardation. Stereotypies are seen in adults with lesions or disorders affecting the frontostriatal circuit running between the dorsolateral frontal cortex and the head of the caudate nucleus. Frontotemporal dementias commonly manifest with stereotypic behaviors resulting from degeneration of the dorsolateral prefrontal cortex. Stimulant medications can produce complex stereotypies through a dopaminergic effect on the basal ganglia. Other repetitive motor behaviors such as compulsive behaviors and tics are seen in patients with Gilles de la Tourette syndrome and obsessive-compulsive disorder, both of which are considered to be associated with basal ganglia pathology. Of importance is that stereotypies, compulsions, complex tics, mannerisms (unusual or pathological styles of performing goal-directed activities, such as a bizarre gait and unusual ways of greeting people), and habits can often be difficult to distinguish purely on the basis of subjective observation. The context and history of the motor phenomena provide important diagnostic information.
Stereotypies are repetitive, rhythmical, and invariant motor behaviors, without an apparent purpose or function, that can vary from simple motor behaviors such as rocking or hand waving to extraordinarily complex acts and rituals. They are one of the defining features of autism and are common in patients with mental retardation. Stereotypies are seen in adults with lesions or disorders affecting the frontostriatal circuit running between the dorsolateral frontal cortex and the head of the caudate nucleus. Frontotemporal dementias commonly manifest with stereotypic behaviors resulting from degeneration of the dorsolateral prefrontal cortex. Stimulant medications can produce complex stereotypies through a dopaminergic effect on the basal ganglia. Other repetitive motor behaviors such as compulsive behaviors and tics are seen in patients with Gilles de la Tourette syndrome and obsessive-compulsive disorder, both of which are considered to be associated with basal ganglia pathology. Of importance is that stereotypies, compulsions, complex tics, mannerisms (unusual or pathological styles of performing goal-directed activities, such as a bizarre gait and unusual ways of greeting people), and habits can often be difficult to distinguish purely on the basis of subjective observation. The context and history of the motor phenomena provide important diagnostic information.
2013年1月23日 星期三
Postictal state of seizure
The following paragraph was taken from UpToDate on 2013/01/23:
Postictal state —Manifestations typically include confusion and suppressed alertness; focal neurologic deficits may also be present. The postictal state may last from seconds to minutes to hours, depending upon several factors including which part(s) of the brain were affected by the seizure, the length of the seizure, whether the individual was on AEDs, and age.
As an example, young adults with partial seizures of frontal lobe origin may have postictal states that last only several seconds, while elderly patients with secondarily generalized seizures may have postictal confusion and sleepiness that persists for as long as several days to a week, particularly if there is underlying brain dysfunction. If a person had a CPS or a convulsion, his or her level of awareness gradually improves during the postictal period, much like a person waking up from anesthesia after an operation.
The ictal and postictal manifestations are different between complex partial seizure and generalized tonic-clonic seizure:
1. Complex partial seizures typically last less than three minutes and may be immediately preceded by a simple partial seizure. Afterward, the patient enters the postictal phase, often characterized by somnolence, confusion, and headache for up to several hours. The patient has no memory of what took place during the seizure other than, perhaps, the aura.
2. A generalized tonic-clonic seizure (also called grand mal seizure, major motor seizure, or convulsion) is the most dramatic type of seizure. It begins with an abrupt loss of consciousness, often in association with a scream or shriek. All of the muscles of the arms and legs as well as the chest and back then become stiff. The patient may begin to appear cyanotic during this tonic phase. After approximately one minute, the muscles begin to jerk and twitch for an additional one to two minutes. During this clonic phase the tongue can be bitten, and frothy and bloody sputum may be seen coming out of the mouth. The postictal phase begins once the twitching movements end. The patient is initially in a deep sleep, breathing deeply, and then gradually wakes up, often complaining of a headache.
End Note: please remember the following sentence…
In some cases, the postictal symptoms may be the presenting clinical feature, when the seizure itself is very brief and/or unwitnessed.
Postictal state —Manifestations typically include confusion and suppressed alertness; focal neurologic deficits may also be present. The postictal state may last from seconds to minutes to hours, depending upon several factors including which part(s) of the brain were affected by the seizure, the length of the seizure, whether the individual was on AEDs, and age.
As an example, young adults with partial seizures of frontal lobe origin may have postictal states that last only several seconds, while elderly patients with secondarily generalized seizures may have postictal confusion and sleepiness that persists for as long as several days to a week, particularly if there is underlying brain dysfunction. If a person had a CPS or a convulsion, his or her level of awareness gradually improves during the postictal period, much like a person waking up from anesthesia after an operation.
The ictal and postictal manifestations are different between complex partial seizure and generalized tonic-clonic seizure:
1. Complex partial seizures typically last less than three minutes and may be immediately preceded by a simple partial seizure. Afterward, the patient enters the postictal phase, often characterized by somnolence, confusion, and headache for up to several hours. The patient has no memory of what took place during the seizure other than, perhaps, the aura.
2. A generalized tonic-clonic seizure (also called grand mal seizure, major motor seizure, or convulsion) is the most dramatic type of seizure. It begins with an abrupt loss of consciousness, often in association with a scream or shriek. All of the muscles of the arms and legs as well as the chest and back then become stiff. The patient may begin to appear cyanotic during this tonic phase. After approximately one minute, the muscles begin to jerk and twitch for an additional one to two minutes. During this clonic phase the tongue can be bitten, and frothy and bloody sputum may be seen coming out of the mouth. The postictal phase begins once the twitching movements end. The patient is initially in a deep sleep, breathing deeply, and then gradually wakes up, often complaining of a headache.
End Note: please remember the following sentence…
In some cases, the postictal symptoms may be the presenting clinical feature, when the seizure itself is very brief and/or unwitnessed.
Difference between temporal and frontal lobe seizure
The following paragraph was taken from UpToDate on 2013/01/23:
Temporal lobe epilepsy
Complex partial seizures are the most common manifestation of mesial TLE. About one-third of patients have secondarily generalized tonic-clonic seizures in addition to complex partial seizures or as their primary seizure type. Only a few patients with mesial TLE develop status epilepticus. Distinctive characteristics of mesial TLE seizures include the following:
1. An “aura” (a simple partial seizure with sensory symptoms) occurs in most patients, often with features that are relatively specific for TLE, including a rising epigastric sensation (often likened to a "roller coaster" sensation), and psychic or experiential phenomena, such as deja vu, jamais vu, or fear. Auras of taste and smell are less common but are also relatively specific for TLE. Auras can occur in isolation as a simple partial seizure or can precede a complex partial seizure. In either case, patients with mesial TLE usually recall the seizure aura.
2. Complex partial seizures usually manifest with a behavioral arrest and staring and last between 30 and 120 seconds. The patients are generally unaware and unresponsive during this period. Occasionally, such patients present with amnestic attacks, but more detailed questioning or observation of the seizures reveal the presence of olfactory hallucinations, other seizure auras, or ictal automatisms.
3. Automatisms are common, occurring in about 60 percent of complex partial seizures of mesial TLE. These are repetitive, stereotyped, purposeless movements. In TLE, they are typically mild, involving the hands (picking, fidgeting, fumbling) and mouth (chewing, lip smacking).
4. Lateralizing features can occur during as well as after a partial complex or secondary generalized seizure. Unilateral automatisms are usually ipsilateral to the seizure focus, while dystonic posturing almost invariably occurs on the contralateral side. Head deviation at seizure onset is usually ipsilateral to the seizure; when it occurs later, it is contralateral. This later head turning also has a more forceful, involuntary appearance and is so-characterized as "versive" (a seizure characterized by sustained, forced conjugate ocular and cephalic and/or truncal deviation). Contralateral clonic activity is relatively unusual. Lateralizing findings in the setting of mesial temporal sclerosis should be interpreted with some caution, as many of these patients have bilateral, independent seizure foci.
5. Less commonly observed behaviors associated with a temporal lobe seizure include ictal speech and vocalizations, affective behaviors (laughing, crying or fear), hypermotor behaviors usually associated with frontal lobe seizures, and so-called "leaving behavior" (walking or running away).
6. Postictal confusion usually lasts minutes, but may be complicated by psychosis. Postictal hemiparesis can occur contralateral to the seizure focus, and postictal aphasia can occur with a seizure emanating from the dominant hemisphere. Nose-wiping, performed by the hand ipsilateral to the focus of seizure onset, is a common postictal event in mesial TLE. Postictal wandering is not specific to TLE, but is seen more often with temporal compared to extratemporal seizures.
Frontal lobe epilepsy
Common characteristics of frontal lobe seizures are short duration (<30 seconds) and predilection for occurrence during sleep. The latter is particularly true for frontal lobe complex partial seizures and supplementary motor seizures. Differentiating nocturnal seizures from parasomnias can be challenging; one study suggests that it is not uncommon for the two to co-exist.
Seizure clusters and status epilepticus (whether partial, complex partial, or generalized) are also more common in frontal lobe epilepsy than with TLE. A postictal state may be brief or absent. Secondary generalization of frontal lobe seizures was at one time thought to be more common than in mesial TLE, but systematic comparisons suggests that this has a similar incidence in both.
Frontal lobe seizure types include:
1. Complex partial seizures are often characterized by hypermotor behaviors (proximal limbs, tonic). These can produce bizarre-looking episodes that may be mistaken for psychogenic nonepileptic seizures.
2. Other features that suggest complex partial seizures of frontal rather than temporal lobe origin include bicycling automatisms as well as pelvic thrusting and other sexual automatisms. Tonic posturing and head and eye deviation (version), usually contralateral to the side of the seizure focus, can occur in some patients. Vocalizations are also very common.
3. While seizure auras are common in frontal lobe epilepsy, they are less ubiquitous than in mesial TLE, and the sensation is often ill-described and typically does not include epigastric phenomenon. Fear and anxiety occur as seizure auras in both TLE and frontal lobe epilepsy.
4. Consciousness may be more preserved in frontal lobe complex partial seizures compared with TLE. Patients often report recall of ictal events even though they are not able to respond, but the accuracy of this reporting is not certain.
5. Focal motor seizures involving the primary motor cortex will produce hemiclonic activity in the contralateral face, arm, or leg. Seizures may be quite focal (isolated to one limb or face) or may spread (or march) to adjacent areas (ie, Jacksonian seizure). Hemiclonic activity is more common in complex partial seizures of frontal origin than with those in TLE.
6. Supplementary motor area seizures typically produce stereotyped asymmetric tonic movements. One example is the "fencing posture," in which the head and eye deviate to the contralateral side, with extension of the contralateral arm and flexion of the ipsilateral arm. The most prominent tonic activity occurs contralateral to the seizure focus. Brief superimposed clonic movements or vocalizations may also occur. Speech arrest may accompany seizures arising from the dominant hemisphere. There may be a somatosensory aura. Despite bilateral tonic movements, consciousness is often preserved unless there is secondary generalization.
7. So-called frontal absence seizures manifest with staring, trance-like states. These seizures originate from the frontopolar or medial frontal regions. These seizures are more prolonged than other seizure types, often lasting several minutes, sometimes hours, or even days.
8. Secondary generalization may occur after any of the above initial ictal manifestations. A minority of patients have secondary generalized seizures that occur without preceding complex partial or motor symptoms.
Temporal lobe epilepsy
Complex partial seizures are the most common manifestation of mesial TLE. About one-third of patients have secondarily generalized tonic-clonic seizures in addition to complex partial seizures or as their primary seizure type. Only a few patients with mesial TLE develop status epilepticus. Distinctive characteristics of mesial TLE seizures include the following:
1. An “aura” (a simple partial seizure with sensory symptoms) occurs in most patients, often with features that are relatively specific for TLE, including a rising epigastric sensation (often likened to a "roller coaster" sensation), and psychic or experiential phenomena, such as deja vu, jamais vu, or fear. Auras of taste and smell are less common but are also relatively specific for TLE. Auras can occur in isolation as a simple partial seizure or can precede a complex partial seizure. In either case, patients with mesial TLE usually recall the seizure aura.
2. Complex partial seizures usually manifest with a behavioral arrest and staring and last between 30 and 120 seconds. The patients are generally unaware and unresponsive during this period. Occasionally, such patients present with amnestic attacks, but more detailed questioning or observation of the seizures reveal the presence of olfactory hallucinations, other seizure auras, or ictal automatisms.
3. Automatisms are common, occurring in about 60 percent of complex partial seizures of mesial TLE. These are repetitive, stereotyped, purposeless movements. In TLE, they are typically mild, involving the hands (picking, fidgeting, fumbling) and mouth (chewing, lip smacking).
4. Lateralizing features can occur during as well as after a partial complex or secondary generalized seizure. Unilateral automatisms are usually ipsilateral to the seizure focus, while dystonic posturing almost invariably occurs on the contralateral side. Head deviation at seizure onset is usually ipsilateral to the seizure; when it occurs later, it is contralateral. This later head turning also has a more forceful, involuntary appearance and is so-characterized as "versive" (a seizure characterized by sustained, forced conjugate ocular and cephalic and/or truncal deviation). Contralateral clonic activity is relatively unusual. Lateralizing findings in the setting of mesial temporal sclerosis should be interpreted with some caution, as many of these patients have bilateral, independent seizure foci.
5. Less commonly observed behaviors associated with a temporal lobe seizure include ictal speech and vocalizations, affective behaviors (laughing, crying or fear), hypermotor behaviors usually associated with frontal lobe seizures, and so-called "leaving behavior" (walking or running away).
6. Postictal confusion usually lasts minutes, but may be complicated by psychosis. Postictal hemiparesis can occur contralateral to the seizure focus, and postictal aphasia can occur with a seizure emanating from the dominant hemisphere. Nose-wiping, performed by the hand ipsilateral to the focus of seizure onset, is a common postictal event in mesial TLE. Postictal wandering is not specific to TLE, but is seen more often with temporal compared to extratemporal seizures.
Frontal lobe epilepsy
Common characteristics of frontal lobe seizures are short duration (<30 seconds) and predilection for occurrence during sleep. The latter is particularly true for frontal lobe complex partial seizures and supplementary motor seizures. Differentiating nocturnal seizures from parasomnias can be challenging; one study suggests that it is not uncommon for the two to co-exist.
Seizure clusters and status epilepticus (whether partial, complex partial, or generalized) are also more common in frontal lobe epilepsy than with TLE. A postictal state may be brief or absent. Secondary generalization of frontal lobe seizures was at one time thought to be more common than in mesial TLE, but systematic comparisons suggests that this has a similar incidence in both.
Frontal lobe seizure types include:
1. Complex partial seizures are often characterized by hypermotor behaviors (proximal limbs, tonic). These can produce bizarre-looking episodes that may be mistaken for psychogenic nonepileptic seizures.
2. Other features that suggest complex partial seizures of frontal rather than temporal lobe origin include bicycling automatisms as well as pelvic thrusting and other sexual automatisms. Tonic posturing and head and eye deviation (version), usually contralateral to the side of the seizure focus, can occur in some patients. Vocalizations are also very common.
3. While seizure auras are common in frontal lobe epilepsy, they are less ubiquitous than in mesial TLE, and the sensation is often ill-described and typically does not include epigastric phenomenon. Fear and anxiety occur as seizure auras in both TLE and frontal lobe epilepsy.
4. Consciousness may be more preserved in frontal lobe complex partial seizures compared with TLE. Patients often report recall of ictal events even though they are not able to respond, but the accuracy of this reporting is not certain.
5. Focal motor seizures involving the primary motor cortex will produce hemiclonic activity in the contralateral face, arm, or leg. Seizures may be quite focal (isolated to one limb or face) or may spread (or march) to adjacent areas (ie, Jacksonian seizure). Hemiclonic activity is more common in complex partial seizures of frontal origin than with those in TLE.
6. Supplementary motor area seizures typically produce stereotyped asymmetric tonic movements. One example is the "fencing posture," in which the head and eye deviate to the contralateral side, with extension of the contralateral arm and flexion of the ipsilateral arm. The most prominent tonic activity occurs contralateral to the seizure focus. Brief superimposed clonic movements or vocalizations may also occur. Speech arrest may accompany seizures arising from the dominant hemisphere. There may be a somatosensory aura. Despite bilateral tonic movements, consciousness is often preserved unless there is secondary generalization.
7. So-called frontal absence seizures manifest with staring, trance-like states. These seizures originate from the frontopolar or medial frontal regions. These seizures are more prolonged than other seizure types, often lasting several minutes, sometimes hours, or even days.
8. Secondary generalization may occur after any of the above initial ictal manifestations. A minority of patients have secondary generalized seizures that occur without preceding complex partial or motor symptoms.
2011年12月11日 星期日
TIA (limb-shaking) or seizure in elderly
The following paragraph was taken from UpToDate on 2011/12/07:
Transient ischemic attacks (TIAs) may be mistaken for seizures, but they may also induce seizures.
Brain ischemia produces reduced neural activity and "negative" symptoms such as hemiparesis or hemisensory loss. In contrast, seizures usually cause "positive" symptoms from neural overactivity. So called "limb-shaking" TIAs may represent a source of diagnostic confusion in this regard. This somewhat unusual manifestation of cerebral ischemia typically occurs in the setting of high-grade carotid stenosis.
Certain symptoms, such as aphasia, can occur in TIA or seizure. While an isolated episode of aphasia is more likely to be a TIA than a seizure, aphasic seizures are well described. In general, ictal aphasia is progressive, developing over minutes from dysphasia to paraphasic errors, and culminating in a global aphasia. In contrast, TIA symptoms develop abruptly and typically do not evolve. Although TIA is commonly considered as a cause for confusional episodes, confusion is rarely a manifestation of TIA.
Chronic, recurrent stereotyped events are much more likely to be seizure than TIA. Transient loss of consciousness only should not be diagnoed as TIA. However, since syncope can rarely occur in association stroke, care should be exercised in the evaluation of patients with syncope and limb weakness which can actually be Todd's paralysis after a seizure of no witness.
Transient ischemic attacks (TIAs) may be mistaken for seizures, but they may also induce seizures.
Brain ischemia produces reduced neural activity and "negative" symptoms such as hemiparesis or hemisensory loss. In contrast, seizures usually cause "positive" symptoms from neural overactivity. So called "limb-shaking" TIAs may represent a source of diagnostic confusion in this regard. This somewhat unusual manifestation of cerebral ischemia typically occurs in the setting of high-grade carotid stenosis.
Certain symptoms, such as aphasia, can occur in TIA or seizure. While an isolated episode of aphasia is more likely to be a TIA than a seizure, aphasic seizures are well described. In general, ictal aphasia is progressive, developing over minutes from dysphasia to paraphasic errors, and culminating in a global aphasia. In contrast, TIA symptoms develop abruptly and typically do not evolve. Although TIA is commonly considered as a cause for confusional episodes, confusion is rarely a manifestation of TIA.
Chronic, recurrent stereotyped events are much more likely to be seizure than TIA. Transient loss of consciousness only should not be diagnoed as TIA. However, since syncope can rarely occur in association stroke, care should be exercised in the evaluation of patients with syncope and limb weakness which can actually be Todd's paralysis after a seizure of no witness.
Dialeptic seizure or syncope in elderly
The following paragraph was taken from UpToDate on 2012/12/07:
Complex partial seizure was the most common seizure type in older patients; 38.3 percent of patients experienced complex partial seizures. In contrast to younger patients, complex partial seizures in older adults are more often extratemporal, usually frontal, in origin, and therefore have an "atypical" clinical presentation. Classic descriptions of seizure aura, such as deja vu and olfactory hallucinations, are uncommon. Patients may instead report antecedent symptoms that are atypical and nonspecific, such as vaguely localized paresthesias, dizziness, and muscle cramps. Observers often note episodic confusion, sleepiness, or clumsiness rather than motor manifestations such as tonic or clonic movements, or automatisms. Postictal states are frequently more prolonged in elderly patients, particularly if there is underlying brain dysfunction.
Because of the "atypical" symptomatology, elderly patients with seizures may be frequently misdiagnosed. In a study, VACS#428, 73.3 percent of patients ultimately diagnosed with epilepsy had a different referral diagnosis. These included altered mental status, confusion, blackout spells, memory disturbance, syncope, dizziness, and dementia. In another series, transient ischemic attack (TIA), depression, and metabolic or psychiatric disorders were also among the initial misdiagnoses. Misdiagnosis is more common in patients with partial complex and partial simple seizures than with generalized tonic-clonic seizures. Despite the known association of seizures and cerebrovascular disease, a history of stroke or TIA was associated with a 1.7-year delay to diagnosis. Similarly, comorbid dementia can obscure the recognition of seizures.
How about syncope? The following description is an extract from Adam’s Neurology:
Description of symptoms, as with other predominantly subjective states, is often ambiguous. The patient may refer to the experience as light-headedness, giddiness, dizziness, a "drunk feeling," a weak spell, or, if consciousness was lost, a "blackout." Careful questioning may be necessary to ascertain the exact meaning the patient has given to these words. In many instances the nature of the symptoms is clarified by the fact that they include a sensation of faintness and then a momentary loss of consciousness, which is easily recognized as a faint, or syncope. This sequence also informs us that under certain conditions any difference between faintness and syncope is only one of degree. These symptoms must be clearly set apart from certain types of epilepsy, the other major cause of episodic unconsciousness, and from disorders such as cataplexy, transient ischemic attacks (TIAs), "drop attacks," and vertigo, which are also characterized by episodic attacks of generalized weakness or inability to stand upright, but not by a loss of consciousness.
The clinical manifestations of fainting attacks vary to some extent, depending on their mechanisms and the settings in which they occur. The most common type of faint—namely, vasodepressor or vasovagal syncope conforms more or less to the following pattern. The patient is usually in the upright position at the beginning of the attack, either sitting or standing. Certain subjective symptoms, the prodrome, mark the onset of the faint. The person feels queasy, is assailed by a sense of giddiness and apprehension, may sway, and sometimes develops a headache. What is most noticeable at the beginning of the attack is pallor or an ashen-gray color of the face; often the face and body become bathed in cool perspiration. Salivation, epigastric distress, nausea, and sometimes vomiting may accompany these symptoms, and the patient tries to suppress them by yawning, sighing, or breathing deeply. Vision may dim or close in concentrically, the ears may ring, and it may be impossible to think clearly ("grayout").
This serves to introduce the common faint that is known to all physicians and most laypersons. However, if there is no such typical presentation, it is challenging to different syncope or faint from dialeptic seizure in the elderly. Seizures are the probable cause of 5 to 15 percent of apparent syncopal episodes. They can mimic syncope when the seizure is atypical and not associated with tonic-clonic movements, the seizure is not observed, or a complete history cannot be obtained. A careful clinical history is important in distinguishing syncope from epilepsy. Important features are not always volunteered and must be specifically solicited.
Features that distinguish syncope from seizures are discussed further on.
Differential diagnosis:
Syncope in an elderly patient can be accompanied by incontinence, and recovery is often slow, mimicking a postictal state. In addition, some patients with syncope present with myoclonic or other involuntary movements that are suggestive of a seizure but are actually due to cerebral hypoxia.
One distinguishing feature is recovery of consciousness. Patients usually wake up quickly after a syncopal event. Prolonged confusion or lethargy lasting several minutes or longer favors seizure.
Clinical setting - Epileptic seizures and syncope arising from cardiac arrhythmias can occur in any setting and are usually unprovoked. Vasovagal syncope tends to occur in the setting of a strong emotional or painful stimulus, but may also occur with more subtle stimuli, including a hot environment. Reflex syncopes occur with specific stimuli (eg, micturition, cough). Events in the setting of exertion suggest syncope related to structural cardiac disease. Except when caused by a cardiac arrhythmia, it is unusual for syncope to occur when patient is supine.
Warning symptoms (aura, prodrome) - In vasovagal syncope, a prodrome of presyncope is the rule. These patients may note lightheadedness, warmth, nausea, and a gradual fading or tunneling of binocular vision. In contrast, symptoms of olfactory hallucinations or deja vu suggest a seizure aura. However, not all epileptic seizures include a seizure aura. Cardiogenic syncope typically occurs without warning.
Associated symptoms - Pallor and diaphoresis strongly suggest syncope. However, it is unusual for syncope to be associated with tongue biting, head or eye turning to one side, or hypersalivation; these suggest epileptic seizure. Urinary incontinence can occur in both seizures and syncope.
Symptoms occurring in association with syncope can point toward a specific cause. As examples, dyspnea may suggest an acute pulmonary embolism; angina frequently indicates an underlying cardiac cause; a history of focal neurologic abnormalities favors a neurologic origin; and urinary and/or fecal incontinence suggest, but do not prove, a seizure.
Motor activity - While motor activity during an episode of unconsciousness often suggests a seizure diagnosis, brief motor activity, including tonic extension of the trunk and limbs or several clonic jerks, can occur in uncomplicated syncope. The severity of convulsive symptoms in syncope varies from subtle signs that are often overlooked to more dramatic symptoms that mimic an epileptic seizure. Relatively few bystanders witnessing syncopal attacks report convulsive symptoms, but clinicians systematically observing attacks (eg, during tilt table testing, invasive cardiac electrophysiologic testing, blood drawing) describe convulsive symptoms in up to half of patients. Convulsions (in syncope) are more likely to occur with more prolonged and more severe cerebral hypoperfusion.
Electroencephalography (EEG) recordings during syncopal events usually demonstrate generalized slowing followed by high voltage frontal delta activity [15,16]. Flattening of the EEG can follow if cerebral hypoperfusion persists. It is at this stage that nonepileptic, seizure-like movements are most often described. It has been suggested that these movements may represent a brainstem-release phenomenon.
The combination of seizure-like motor activity in the setting of syncope is sometimes referred to as convulsive syncope. While these convulsions are common in syncope, a true epileptic seizure ("anoxic seizure") is rare, except in susceptible people or those with prolonged cerebral ischemia.
Complex partial seizure was the most common seizure type in older patients; 38.3 percent of patients experienced complex partial seizures. In contrast to younger patients, complex partial seizures in older adults are more often extratemporal, usually frontal, in origin, and therefore have an "atypical" clinical presentation. Classic descriptions of seizure aura, such as deja vu and olfactory hallucinations, are uncommon. Patients may instead report antecedent symptoms that are atypical and nonspecific, such as vaguely localized paresthesias, dizziness, and muscle cramps. Observers often note episodic confusion, sleepiness, or clumsiness rather than motor manifestations such as tonic or clonic movements, or automatisms. Postictal states are frequently more prolonged in elderly patients, particularly if there is underlying brain dysfunction.
Because of the "atypical" symptomatology, elderly patients with seizures may be frequently misdiagnosed. In a study, VACS#428, 73.3 percent of patients ultimately diagnosed with epilepsy had a different referral diagnosis. These included altered mental status, confusion, blackout spells, memory disturbance, syncope, dizziness, and dementia. In another series, transient ischemic attack (TIA), depression, and metabolic or psychiatric disorders were also among the initial misdiagnoses. Misdiagnosis is more common in patients with partial complex and partial simple seizures than with generalized tonic-clonic seizures. Despite the known association of seizures and cerebrovascular disease, a history of stroke or TIA was associated with a 1.7-year delay to diagnosis. Similarly, comorbid dementia can obscure the recognition of seizures.
How about syncope? The following description is an extract from Adam’s Neurology:
Description of symptoms, as with other predominantly subjective states, is often ambiguous. The patient may refer to the experience as light-headedness, giddiness, dizziness, a "drunk feeling," a weak spell, or, if consciousness was lost, a "blackout." Careful questioning may be necessary to ascertain the exact meaning the patient has given to these words. In many instances the nature of the symptoms is clarified by the fact that they include a sensation of faintness and then a momentary loss of consciousness, which is easily recognized as a faint, or syncope. This sequence also informs us that under certain conditions any difference between faintness and syncope is only one of degree. These symptoms must be clearly set apart from certain types of epilepsy, the other major cause of episodic unconsciousness, and from disorders such as cataplexy, transient ischemic attacks (TIAs), "drop attacks," and vertigo, which are also characterized by episodic attacks of generalized weakness or inability to stand upright, but not by a loss of consciousness.
The clinical manifestations of fainting attacks vary to some extent, depending on their mechanisms and the settings in which they occur. The most common type of faint—namely, vasodepressor or vasovagal syncope conforms more or less to the following pattern. The patient is usually in the upright position at the beginning of the attack, either sitting or standing. Certain subjective symptoms, the prodrome, mark the onset of the faint. The person feels queasy, is assailed by a sense of giddiness and apprehension, may sway, and sometimes develops a headache. What is most noticeable at the beginning of the attack is pallor or an ashen-gray color of the face; often the face and body become bathed in cool perspiration. Salivation, epigastric distress, nausea, and sometimes vomiting may accompany these symptoms, and the patient tries to suppress them by yawning, sighing, or breathing deeply. Vision may dim or close in concentrically, the ears may ring, and it may be impossible to think clearly ("grayout").
This serves to introduce the common faint that is known to all physicians and most laypersons. However, if there is no such typical presentation, it is challenging to different syncope or faint from dialeptic seizure in the elderly. Seizures are the probable cause of 5 to 15 percent of apparent syncopal episodes. They can mimic syncope when the seizure is atypical and not associated with tonic-clonic movements, the seizure is not observed, or a complete history cannot be obtained. A careful clinical history is important in distinguishing syncope from epilepsy. Important features are not always volunteered and must be specifically solicited.
Features that distinguish syncope from seizures are discussed further on.
Differential diagnosis:
Syncope in an elderly patient can be accompanied by incontinence, and recovery is often slow, mimicking a postictal state. In addition, some patients with syncope present with myoclonic or other involuntary movements that are suggestive of a seizure but are actually due to cerebral hypoxia.
One distinguishing feature is recovery of consciousness. Patients usually wake up quickly after a syncopal event. Prolonged confusion or lethargy lasting several minutes or longer favors seizure.
Clinical setting - Epileptic seizures and syncope arising from cardiac arrhythmias can occur in any setting and are usually unprovoked. Vasovagal syncope tends to occur in the setting of a strong emotional or painful stimulus, but may also occur with more subtle stimuli, including a hot environment. Reflex syncopes occur with specific stimuli (eg, micturition, cough). Events in the setting of exertion suggest syncope related to structural cardiac disease. Except when caused by a cardiac arrhythmia, it is unusual for syncope to occur when patient is supine.
Warning symptoms (aura, prodrome) - In vasovagal syncope, a prodrome of presyncope is the rule. These patients may note lightheadedness, warmth, nausea, and a gradual fading or tunneling of binocular vision. In contrast, symptoms of olfactory hallucinations or deja vu suggest a seizure aura. However, not all epileptic seizures include a seizure aura. Cardiogenic syncope typically occurs without warning.
Associated symptoms - Pallor and diaphoresis strongly suggest syncope. However, it is unusual for syncope to be associated with tongue biting, head or eye turning to one side, or hypersalivation; these suggest epileptic seizure. Urinary incontinence can occur in both seizures and syncope.
Symptoms occurring in association with syncope can point toward a specific cause. As examples, dyspnea may suggest an acute pulmonary embolism; angina frequently indicates an underlying cardiac cause; a history of focal neurologic abnormalities favors a neurologic origin; and urinary and/or fecal incontinence suggest, but do not prove, a seizure.
Motor activity - While motor activity during an episode of unconsciousness often suggests a seizure diagnosis, brief motor activity, including tonic extension of the trunk and limbs or several clonic jerks, can occur in uncomplicated syncope. The severity of convulsive symptoms in syncope varies from subtle signs that are often overlooked to more dramatic symptoms that mimic an epileptic seizure. Relatively few bystanders witnessing syncopal attacks report convulsive symptoms, but clinicians systematically observing attacks (eg, during tilt table testing, invasive cardiac electrophysiologic testing, blood drawing) describe convulsive symptoms in up to half of patients. Convulsions (in syncope) are more likely to occur with more prolonged and more severe cerebral hypoperfusion.
Electroencephalography (EEG) recordings during syncopal events usually demonstrate generalized slowing followed by high voltage frontal delta activity [15,16]. Flattening of the EEG can follow if cerebral hypoperfusion persists. It is at this stage that nonepileptic, seizure-like movements are most often described. It has been suggested that these movements may represent a brainstem-release phenomenon.
The combination of seizure-like motor activity in the setting of syncope is sometimes referred to as convulsive syncope. While these convulsions are common in syncope, a true epileptic seizure ("anoxic seizure") is rare, except in susceptible people or those with prolonged cerebral ischemia.
2011年7月10日 星期日
EEG Patterns and Imaging Correlations
This is a very nice article.
I have been expecting it for a long time.
The author is Kaplan et al.
The following is its abstract.
The EEG patterns seen with encephalopathies can be correlated to cerebral imaging findings including head computerized tomography and MRI. Background slowing without slow-wave intrusion is seen with acute and chronic cortical impairments that spare subcortical white matter. Subcortical/white matter structural abnormalities or hydrocephalus may produce projected slow-wave activity, while clinical entities involving both cortical and subcortical regions (diffuse cerebral abnormalities) engender both background slowing and slow-wave activity. Triphasic waves are seen with hepatic and renal insufficiency or medication toxicities (e.g., lithium, baclofen) in the absence of a significant cerebral imaging abnormality, Conversely, subcortical/white matter abnormalities may facilitate the appearance of triphasic waves without significant hepatic, renal, or toxic comorbidities. More specific syndromes, such as Jakob-Creutzfeldt disease, autoimmune limbic encephalitis, autoimmune corticosteroid-responsive encephalopathy with thyroid autoimmunity, sepsis-associated encephalopathy, and acute disseminated encephalomyelitis, have imaging/EEG changes that are variable but which may include slowing and epileptiform activity. This overview highlighting EEG-imaging correlations may help the treating physician in the diagnosis, and hence the appropriate treatment, of patients with encephalopathy.
Reference:
P. W. Kaplan and A. O. Rossetti. EEG Patterns and Imaging Correlations in Encephalopathy: Encephalopathy Part II. J Clin Neurophysiol. 2011 Jun;28(3):233-51.
I have been expecting it for a long time.
The author is Kaplan et al.
The following is its abstract.
The EEG patterns seen with encephalopathies can be correlated to cerebral imaging findings including head computerized tomography and MRI. Background slowing without slow-wave intrusion is seen with acute and chronic cortical impairments that spare subcortical white matter. Subcortical/white matter structural abnormalities or hydrocephalus may produce projected slow-wave activity, while clinical entities involving both cortical and subcortical regions (diffuse cerebral abnormalities) engender both background slowing and slow-wave activity. Triphasic waves are seen with hepatic and renal insufficiency or medication toxicities (e.g., lithium, baclofen) in the absence of a significant cerebral imaging abnormality, Conversely, subcortical/white matter abnormalities may facilitate the appearance of triphasic waves without significant hepatic, renal, or toxic comorbidities. More specific syndromes, such as Jakob-Creutzfeldt disease, autoimmune limbic encephalitis, autoimmune corticosteroid-responsive encephalopathy with thyroid autoimmunity, sepsis-associated encephalopathy, and acute disseminated encephalomyelitis, have imaging/EEG changes that are variable but which may include slowing and epileptiform activity. This overview highlighting EEG-imaging correlations may help the treating physician in the diagnosis, and hence the appropriate treatment, of patients with encephalopathy.
Reference:
P. W. Kaplan and A. O. Rossetti. EEG Patterns and Imaging Correlations in Encephalopathy: Encephalopathy Part II. J Clin Neurophysiol. 2011 Jun;28(3):233-51.
Chronic kidney disease and stroke
Chronic kidney disease (CKD) increases cardiovascular (CV) disease risk, including transient ischemic attacks (TIA) and stroke. ESRD is associated with a 10- to 20-fold larger rate of CV mortality and advanced carotid atherosclerosis compared with the general population. In the British Regional Heart Study a serum creatinine level over 1.3 mg/dL significantly increased the risk of stroke, even after adjustment for several CV risk factors. Among patients with isolated systolic hypertension, higher creatinine levels increased the odds-ratio (OR) for stroke.
Lacunar silent brain infarcts correlate independently to estimated declining glomerular filtration rates (GFR). A glance at less advanced renal dysfunction in selected patients with chronic heart disease followed-up for incidental ischemic stroke or TIA over years showed that those with CKD (ie eGFR<60 mL/min/1.73 m2) had a 1.54-fold OR (CI 95%:1.13 to 2.09) of incident ischemic stroke and TIA. Cumulative ischemic stroke or TIA-free curves decline by increasing serum creatinine levels. Increased CV risk is explained by anemia, oxidative stress, hypercalcemia, hyperphosphatemia and secondary hyperparathyroidism, increased homocysteine, inflammation, atherosclerosis, endothelial dysfunction, and coagulation promotion; this last one most associated with nephrotic syndrome.
In nephrotic syndrome, prophylactic anticoagulation is recommended when plasma albumin is below 3 g/dL.
Intracerebral, subdural, and subarachnoid hemorrhage (SAH) yield a mortality index of up to 60% in CKD. It is related to platelet dysfunction, altered platelet-vessel wall interaction, arterial hypertension, head trauma, polycystic kidney disease, use of anticoagulants, and platelet antiaggregants. Subdural hematomas may clinically resemble encephalopathy. Management includes minimal or heparin-free HD, switch from HD to PD (not requiring anticoagulation), and surgery.
Reference:
Lacerda et al. Neurologic Presentations of Renal Diseases. Neurol Clin 28 (2010) 45–59.
Lacunar silent brain infarcts correlate independently to estimated declining glomerular filtration rates (GFR). A glance at less advanced renal dysfunction in selected patients with chronic heart disease followed-up for incidental ischemic stroke or TIA over years showed that those with CKD (ie eGFR<60 mL/min/1.73 m2) had a 1.54-fold OR (CI 95%:1.13 to 2.09) of incident ischemic stroke and TIA. Cumulative ischemic stroke or TIA-free curves decline by increasing serum creatinine levels. Increased CV risk is explained by anemia, oxidative stress, hypercalcemia, hyperphosphatemia and secondary hyperparathyroidism, increased homocysteine, inflammation, atherosclerosis, endothelial dysfunction, and coagulation promotion; this last one most associated with nephrotic syndrome.
In nephrotic syndrome, prophylactic anticoagulation is recommended when plasma albumin is below 3 g/dL.
Intracerebral, subdural, and subarachnoid hemorrhage (SAH) yield a mortality index of up to 60% in CKD. It is related to platelet dysfunction, altered platelet-vessel wall interaction, arterial hypertension, head trauma, polycystic kidney disease, use of anticoagulants, and platelet antiaggregants. Subdural hematomas may clinically resemble encephalopathy. Management includes minimal or heparin-free HD, switch from HD to PD (not requiring anticoagulation), and surgery.
Reference:
Lacerda et al. Neurologic Presentations of Renal Diseases. Neurol Clin 28 (2010) 45–59.
2010年10月7日 星期四
EPILEPSY IN THE ELDERLY
CLINICAL PRESENTATION — Most seizures in elderly patients are partial onset, with or without secondary generalization. When generalized, the partial onset may be unobserved or unrecognized, and the patient incorrectly classified as having primary generalized seizures. Late-onset primary generalized epilepsy, while rare, has been described in older individuals. It is possible that these were lifelong conditions, previously undiagnosed.
Complex partial seizure was the most common seizure type in older patients in the VACS#428 (a clinical trial of antiepileptic medications in elderly people with epilepsy); 38.3 percent of patients experienced complex partial seizures. In contrast to younger patients, complex partial seizures in the elderly are more often extratemporal, usually frontal, in origin, and therefore have an "atypical" clinical presentation. Classic descriptions of seizure aura, such as deja vu and olfactory hallucinations, are uncommon. Patients may instead report antecedent symptoms that are atypical and nonspecific, such as vaguely localized paresthesias, dizziness, and muscle cramps. Observers often note episodic confusion, sleepiness, or clumsiness rather than motor manifestations such as tonic or clonic movements, or automatisms. Postictal states are frequently more prolonged in elderly patients.
Because of the "atypical" symptomatology, elderly patients with seizures may be frequently misdiagnosed. In the VACS#428, 73.3 percent of patients ultimately diagnosed with epilepsy had a different referral diagnosis. These included altered mental status, confusion, blackout spells, memory disturbance, syncope, dizziness, and dementia. In another series, transient ischemic attack (TIA), depression, and metabolic or psychiatric disorders were also among the initial misdiagnoses. Misdiagnosis is more common in patients with partial complex and partial simple seizures than with generalized tonic-clonic seizures. Despite the known association of seizures and cerebrovascular disease, a history of stroke or TIA was associated with a 1.7-year delay to diagnosis. Similarly, comorbid dementia can obscure the recognition of seizures.
Dementia and epilepsy — Alzheimer disease (AD) is a risk factor for epilepsy. Between 9 to 16 percent of patients with AD will develop seizures, usually in the later stages of disease, a rate 10 times otherwise expected. A premorbid diagnosis of either AD or non-Alzheimer dementia are more common in patients presenting with a first unprovoked seizure compared with age-matched hospitalized controls (OR=6 and 8, respectively). A prospective cohort study of 233 patients with newly diagnosed AD found that younger age at onset and more severe dementia were independent risk factors for incident epilepsy.
Seizures in the setting of dementia account for 9 to 17 percent of elderly people with epilepsy. Dementia may coexist and possibly interact with other causes of epilepsy. In a prospective study, preexisting dementia increased the risk of post-stroke epilepsy. In another retrospective case series, 40 percent of patients with dementia and seizures had another potential structural cause (usually stroke) for their seizures.
IMPORTANT DIFFERENTIAL DIAGNOSIS
Delirium or acute toxic-metabolic encephalopathy may be difficult to distinguish from partial complex seizures and nonconvulsive status epilepticus (NCSE), particularly in a patient with baseline neurologic impairment. Episodic, dramatic changes in mental status with a return to normal or baseline cognition strongly suggest seizures, but the presentation may be more subtle.
When present, stereotyped motor movements or automatisms suggest seizure. However, tremor, asterixis, and myoclonus are not uncommon in delirium. Hallucinations may be a feature of either condition. Causes of delirium and seizures overlap, and delirium and seizures can coexist. EEG can identify or exclude seizures in this setting.
SUMMARY AND RECOMMENDATIONS
• A first seizure is not uncommon in elderly persons and can represent an acute symptomatic seizure, a provoked event that is not expected to recur in the absence of that trigger or new-onset epilepsy, a condition in which recurrent unprovoked seizures are expected in the absence of treatment.
• In this age group, acute symptomatic seizures are most often seen in the setting of acute stroke and metabolic encephalopathy. Cerebrovascular disease and degenerative dementia are common causes of epilepsy in the elderly, but one-third to one-half of cases are of cryptogenic origin.
• The overwhelming majority of late-onset epilepsy is partial or localization-related and presents with partial complex seizures, with and without secondary generalization.
• Clinicians should maintain a high level of suspicion for possible seizures in older patients presenting with intermittent or fluctuating confusional states. The usual clues to the possibility of underlying seizures are often absent.
• Considerations in the differential diagnosis of seizures in older patients include syncope and transient cerebral ischemia, as well as other disorders.
Reference:
http://www.uptodate.com/online/content/topic.do?topicKey=epil_eeg/6024&selectedTitle=2%7E150&source=search_result
available on 10/06/2010
Complex partial seizure was the most common seizure type in older patients in the VACS#428 (a clinical trial of antiepileptic medications in elderly people with epilepsy); 38.3 percent of patients experienced complex partial seizures. In contrast to younger patients, complex partial seizures in the elderly are more often extratemporal, usually frontal, in origin, and therefore have an "atypical" clinical presentation. Classic descriptions of seizure aura, such as deja vu and olfactory hallucinations, are uncommon. Patients may instead report antecedent symptoms that are atypical and nonspecific, such as vaguely localized paresthesias, dizziness, and muscle cramps. Observers often note episodic confusion, sleepiness, or clumsiness rather than motor manifestations such as tonic or clonic movements, or automatisms. Postictal states are frequently more prolonged in elderly patients.
Because of the "atypical" symptomatology, elderly patients with seizures may be frequently misdiagnosed. In the VACS#428, 73.3 percent of patients ultimately diagnosed with epilepsy had a different referral diagnosis. These included altered mental status, confusion, blackout spells, memory disturbance, syncope, dizziness, and dementia. In another series, transient ischemic attack (TIA), depression, and metabolic or psychiatric disorders were also among the initial misdiagnoses. Misdiagnosis is more common in patients with partial complex and partial simple seizures than with generalized tonic-clonic seizures. Despite the known association of seizures and cerebrovascular disease, a history of stroke or TIA was associated with a 1.7-year delay to diagnosis. Similarly, comorbid dementia can obscure the recognition of seizures.
Dementia and epilepsy — Alzheimer disease (AD) is a risk factor for epilepsy. Between 9 to 16 percent of patients with AD will develop seizures, usually in the later stages of disease, a rate 10 times otherwise expected. A premorbid diagnosis of either AD or non-Alzheimer dementia are more common in patients presenting with a first unprovoked seizure compared with age-matched hospitalized controls (OR=6 and 8, respectively). A prospective cohort study of 233 patients with newly diagnosed AD found that younger age at onset and more severe dementia were independent risk factors for incident epilepsy.
Seizures in the setting of dementia account for 9 to 17 percent of elderly people with epilepsy. Dementia may coexist and possibly interact with other causes of epilepsy. In a prospective study, preexisting dementia increased the risk of post-stroke epilepsy. In another retrospective case series, 40 percent of patients with dementia and seizures had another potential structural cause (usually stroke) for their seizures.
IMPORTANT DIFFERENTIAL DIAGNOSIS
Delirium or acute toxic-metabolic encephalopathy may be difficult to distinguish from partial complex seizures and nonconvulsive status epilepticus (NCSE), particularly in a patient with baseline neurologic impairment. Episodic, dramatic changes in mental status with a return to normal or baseline cognition strongly suggest seizures, but the presentation may be more subtle.
When present, stereotyped motor movements or automatisms suggest seizure. However, tremor, asterixis, and myoclonus are not uncommon in delirium. Hallucinations may be a feature of either condition. Causes of delirium and seizures overlap, and delirium and seizures can coexist. EEG can identify or exclude seizures in this setting.
SUMMARY AND RECOMMENDATIONS
• A first seizure is not uncommon in elderly persons and can represent an acute symptomatic seizure, a provoked event that is not expected to recur in the absence of that trigger or new-onset epilepsy, a condition in which recurrent unprovoked seizures are expected in the absence of treatment.
• In this age group, acute symptomatic seizures are most often seen in the setting of acute stroke and metabolic encephalopathy. Cerebrovascular disease and degenerative dementia are common causes of epilepsy in the elderly, but one-third to one-half of cases are of cryptogenic origin.
• The overwhelming majority of late-onset epilepsy is partial or localization-related and presents with partial complex seizures, with and without secondary generalization.
• Clinicians should maintain a high level of suspicion for possible seizures in older patients presenting with intermittent or fluctuating confusional states. The usual clues to the possibility of underlying seizures are often absent.
• Considerations in the differential diagnosis of seizures in older patients include syncope and transient cerebral ischemia, as well as other disorders.
Reference:
http://www.uptodate.com/online/content/topic.do?topicKey=epil_eeg/6024&selectedTitle=2%7E150&source=search_result
available on 10/06/2010
2010年3月7日 星期日
Primary Progressive Aphasia
Primary progressive aphasia (PPA) 這個名詞是由Mesulam所提出來的。Mesulam在2007年底寫過一篇文章，回溯PPA的發現及發展的經過。故事得要從1975年說起。當時Norman Geschwind離開Boston City Hospital，到Berth Israel Hospital打算成立Behavioral Neurology Unit (BNU) 。Geschwind把剛受完住院醫師訓練的Mesulam也帶到Berth Israel Hospital。BNU以兩類研究取勝，一類是針對阿茲海默症病患，另一則是對中風之後的失語症所做的研究。Mesulam當時注意到一些病人，乍看之下像Broca aphasia，但若仔細看卻又不是典型的Broca aphasia。病人非但沒有dysarthria，也不曾發生過中風，而其病程卻是一直變壞。基於持續惡化的病程，這些病人一直被認為是罹患了阿茲海默症。但是Mesulam能察人之所不察，注意到一個被其他醫師所忽視的重點。他發現：有的病人實在沒有任何記憶力方面的問題。
開始注意到這種情況之後，BNU很快地就收集了更多的病人。專家學者們也愈來愈感到困惑，最後不得不動手替一位病人做腦組織的病理檢查。也不曉得是福還是禍，其結果根本不符阿茲海默症的病理變化。我猜測，當時的報告如果翻譯成中文，應該就是三個字：見鬼了。更令我好奇的是，BNU裡的專家學者們怎麼向病人解釋這個結果？他們發現了一個新疾病，這個病非但老師沒教過，而且在當時的教科書上也沒寫。接下來怎麼辦？倘若今昔相易，以時下的工具，大家必定會上網用PubMed來查。不過在那時候還沒這玩意兒，Mesulam只好上圖書館搜尋文獻。Mesulam說他接著就在哈佛大學County Library的地下室裡找了數星期。雖然他只是輕描淡寫地說了這麼一句，我很能夠體會其中的艱辛，因為我也曾在同一個地方做過類似的傻事。我曾在那些舊書堆裡待了好幾天，就為了找出罹患椎動脈剝離的最早案例。而今回想起來，那地方還真的有些恐怖：不僅人跡罕至，而且燈光幽暗。突然出現一個人，常把我嚇一大跳。
Mesulam辛苦地找了好幾個星期，先是找到一篇1892年由Pick所寫的文章，其中記載Pick在1891年11月11日遇到的一個病人。這個病人的症狀是三年來失語的情況日益嚴重，類似Mesulam所見。但是這個病人曾經拿刀子恐嚇過他太太，所以Mesulam認為，Pick所描述的這位病人，與自己所見的不一樣。他鍥而不捨，繼續搜尋文獻。接下來，他找到一篇文獻，記載Paul Sérieux在1891年3月11日所見的類似案例。這位女病人在1897年去世，她的腦子由Dejerine來負責解剖及切片檢查，病理報告是bitemporal cortical atrophy及neuronal loss。至此雖稍有斬獲，卻難以結論。因為Alzheimer大約在10年之後才提出阿茲海默症的病理變化，所以這位女病人是否屬於Mesulam所見的那群病人，或只是一位罹患阿茲海默症的患者，若僅依其當時的病理報告，難有定論。
因緣際會。Mesulam偶然與Andre Roch Lecours談論到自己所遇到的案例，也提到了Dejerine / Sérieux那位病人的診斷其實也不確定。數月之後，Andre特地從加拿大飛到Boston，帶給Mesulam一份驚喜。Andre說他透過一些不足為外人道的門路，“借”到了Dejerine當時製作的玻片。Mesulam說他見到了這份上天賜予的禮物，也不敢見獵心喜，冒然將蓋玻片打開，用先進的染色方法去重新染色。因為如果這麼做，Dejerine的玻片就毀了。這借來的荊州，也就不必還了。Mesulam說他臨淵履薄，謹慎小心地看過玻片，確定其中沒有senile plagues也沒有neurofibrillary tangles。所以Mesulam認為Dejerine / Sérieux所描述的病人，應該是他所能找到的最早的案例。
溫故而知新，可以為師矣。Mesulam一方面借助於文獻，另一方面收集更多的病患，在1982年以 “Slowly Progressive Aphasia Without Generalized Dementia”為名，報告6位病例，發表在Annuals of Neurology。Mesulam用progressive這個字，是為了有別於中風，而再冠上slowly一字，是為了表示其病程比腦腫瘤還慢。至於用without generalized dementia，則是為了有別於阿茲海默症。在該文獻中，除了描述這群病人的語言情況之外，Mesulam也提出一個新名詞叫 “logopenia”來描述這群病人的特殊語言表現。
累積更多的經驗之後，Mesulam覺得原來的名字太冗長，遂萌生“正名”之意。正巧在1987年Kirschner報告兩個類似的案例，其腦組織呈現海綿樣的病變。當時Annuals of Neurology雜誌主編Art Asbury邀請Mesulam寫一篇短評。於是Mesulam藉機提出Primary Progressive Aphasia這個名詞。正名之後，Mesulam與 Sandra Weintraub 於1992年在診斷條件中，加入一個 “2年” 的規定 (2-year rule)。其原意，一方面是為了排除Creutzfeldt-Jakob Disease這一類急速惡化的失智症，另一方面則是希望在臨床上能與重度的阿茲海默症病患有所區別。然而，連Mesulam自己也必須承認，在解釋這個規定時，採自由心證，因為要指出發生語言障礙的確切時日，幾乎是不可能的事。
顧名思義，在PPA這個名詞裡，A這個字母是表示患者發生語言方面的症狀，其語言障礙可以是流暢型的失語症，也可以是不流暢型的失語症。Progressive 一字不僅意指失語症係因退化所致，也意味著其病程的進展是以年來計，不至於快到以月來計。 令我感到意外的是Primary一字，竟然是指在疾病初期，病人的主要表現是失語症，而其他的認知功能皆正常。說了半天，我只是為了要把PPA的第一個字“primary” 說清楚。我以前一直以為primary指的是找不出原因，所以叫做 primary。經由Mesulam自己的解說，我才知道Mesulam所謂的primary，並不是我過去所認定的primary。
開始注意到這種情況之後，BNU很快地就收集了更多的病人。專家學者們也愈來愈感到困惑，最後不得不動手替一位病人做腦組織的病理檢查。也不曉得是福還是禍，其結果根本不符阿茲海默症的病理變化。我猜測，當時的報告如果翻譯成中文，應該就是三個字：見鬼了。更令我好奇的是，BNU裡的專家學者們怎麼向病人解釋這個結果？他們發現了一個新疾病，這個病非但老師沒教過，而且在當時的教科書上也沒寫。接下來怎麼辦？倘若今昔相易，以時下的工具，大家必定會上網用PubMed來查。不過在那時候還沒這玩意兒，Mesulam只好上圖書館搜尋文獻。Mesulam說他接著就在哈佛大學County Library的地下室裡找了數星期。雖然他只是輕描淡寫地說了這麼一句，我很能夠體會其中的艱辛，因為我也曾在同一個地方做過類似的傻事。我曾在那些舊書堆裡待了好幾天，就為了找出罹患椎動脈剝離的最早案例。而今回想起來，那地方還真的有些恐怖：不僅人跡罕至，而且燈光幽暗。突然出現一個人，常把我嚇一大跳。
Mesulam辛苦地找了好幾個星期，先是找到一篇1892年由Pick所寫的文章，其中記載Pick在1891年11月11日遇到的一個病人。這個病人的症狀是三年來失語的情況日益嚴重，類似Mesulam所見。但是這個病人曾經拿刀子恐嚇過他太太，所以Mesulam認為，Pick所描述的這位病人，與自己所見的不一樣。他鍥而不捨，繼續搜尋文獻。接下來，他找到一篇文獻，記載Paul Sérieux在1891年3月11日所見的類似案例。這位女病人在1897年去世，她的腦子由Dejerine來負責解剖及切片檢查，病理報告是bitemporal cortical atrophy及neuronal loss。至此雖稍有斬獲，卻難以結論。因為Alzheimer大約在10年之後才提出阿茲海默症的病理變化，所以這位女病人是否屬於Mesulam所見的那群病人，或只是一位罹患阿茲海默症的患者，若僅依其當時的病理報告，難有定論。
因緣際會。Mesulam偶然與Andre Roch Lecours談論到自己所遇到的案例，也提到了Dejerine / Sérieux那位病人的診斷其實也不確定。數月之後，Andre特地從加拿大飛到Boston，帶給Mesulam一份驚喜。Andre說他透過一些不足為外人道的門路，“借”到了Dejerine當時製作的玻片。Mesulam說他見到了這份上天賜予的禮物，也不敢見獵心喜，冒然將蓋玻片打開，用先進的染色方法去重新染色。因為如果這麼做，Dejerine的玻片就毀了。這借來的荊州，也就不必還了。Mesulam說他臨淵履薄，謹慎小心地看過玻片，確定其中沒有senile plagues也沒有neurofibrillary tangles。所以Mesulam認為Dejerine / Sérieux所描述的病人，應該是他所能找到的最早的案例。
溫故而知新，可以為師矣。Mesulam一方面借助於文獻，另一方面收集更多的病患，在1982年以 “Slowly Progressive Aphasia Without Generalized Dementia”為名，報告6位病例，發表在Annuals of Neurology。Mesulam用progressive這個字，是為了有別於中風，而再冠上slowly一字，是為了表示其病程比腦腫瘤還慢。至於用without generalized dementia，則是為了有別於阿茲海默症。在該文獻中，除了描述這群病人的語言情況之外，Mesulam也提出一個新名詞叫 “logopenia”來描述這群病人的特殊語言表現。
累積更多的經驗之後，Mesulam覺得原來的名字太冗長，遂萌生“正名”之意。正巧在1987年Kirschner報告兩個類似的案例，其腦組織呈現海綿樣的病變。當時Annuals of Neurology雜誌主編Art Asbury邀請Mesulam寫一篇短評。於是Mesulam藉機提出Primary Progressive Aphasia這個名詞。正名之後，Mesulam與 Sandra Weintraub 於1992年在診斷條件中，加入一個 “2年” 的規定 (2-year rule)。其原意，一方面是為了排除Creutzfeldt-Jakob Disease這一類急速惡化的失智症，另一方面則是希望在臨床上能與重度的阿茲海默症病患有所區別。然而，連Mesulam自己也必須承認，在解釋這個規定時，採自由心證，因為要指出發生語言障礙的確切時日，幾乎是不可能的事。
顧名思義，在PPA這個名詞裡，A這個字母是表示患者發生語言方面的症狀，其語言障礙可以是流暢型的失語症，也可以是不流暢型的失語症。Progressive 一字不僅意指失語症係因退化所致，也意味著其病程的進展是以年來計，不至於快到以月來計。 令我感到意外的是Primary一字，竟然是指在疾病初期，病人的主要表現是失語症，而其他的認知功能皆正常。說了半天，我只是為了要把PPA的第一個字“primary” 說清楚。我以前一直以為primary指的是找不出原因，所以叫做 primary。經由Mesulam自己的解說，我才知道Mesulam所謂的primary，並不是我過去所認定的primary。
Semantic Dementia
Semantic dementia 這個名詞雖是由 Snowden，Goulding及Neary等人於1989年共同提出，但故事通常得由 Elizabeth Warrington 談起。
Warrington 於1975年以 “selective impairment of semantic memory” 為題，報告3個案例，病人的表現包括 anomia, transcortical sensory aphasia及visual associative agnosia。其中2個病人的腦組織具有 Pick disease 相同的病理變化。然而 Pick 本人是否研究過這個問題？答案是：有！早在1892年 Pick 就談論過腦子裡 meaning system 的理論架構。只不過 Pick 當時所言，而今已成古調，時下皆不談。後人僅記得他所描述的那一群額葉退化的病患，以致於他在這方面的貢獻，也被人遺忘了。
關於 semantic dementia，遠可溯及 Pick，近則與 Tulving 有關。Tulving 提出了episodic memory 及 semantic memory 的假說，Warrington 採納 Tulving 所言，並且認為她所看到的病人是 semantic memory 受損所致。她的想法，說穿了就只有一句話：曾經滄海，才會難為水。只有見過好東西的人，才知道什麼是精緻。舉例而言，semantic dementia 的病人在語言上會有 anomia 的情況。而 Warrington 認為，病人之所以會講不出物品的名稱，表面上是語言的問題，實際上是因為病患心裡根本不存有該物品的意象。連基本的概念都沒有，病人當然就視若無睹。於是病人看到東西，卻說不出其名稱，這就是 anomia。病人若看到文字，卻不曉得是什麼字，表現上就是對 word comprehension 出了問題。Schwartz，Marin 及 Saffran 曾在 1979 年報告過一位這樣的病人：患者可以朗讀，卻完全不了解自己在唸些什麼，典型的 “唸冊歌”。 Mesulam 提出 Primary Progressive Aphasia (PPA) 這個名詞之後， PPA 可以略分為說話流利及不流利兩大類。其中流利型的 PPA，與 Warrington 或 Pick 所報告的是相同的情況。
我們慣於將病患的認知功能分為 memory, attention, language, executive function, higher sensory perception, praxis 等領域來分析。然而若由 semantic dementia 的病患表現，就能了解這些領域並非完全獨立，彼此之間是相關的。名為 semantic memory 的問題，然而患者表現包括 aphasia 及 agnosia。Semantic dementia 病人的表現，令我連想到朱迺欣教授的一段話：如果負責語言功能的 Broca area，並不是像教科書所說，具有固定的部位，那麼所謂的 “左腦語言中樞說” 還會有意義嗎？
大哉斯言。
Warrington 於1975年以 “selective impairment of semantic memory” 為題，報告3個案例，病人的表現包括 anomia, transcortical sensory aphasia及visual associative agnosia。其中2個病人的腦組織具有 Pick disease 相同的病理變化。然而 Pick 本人是否研究過這個問題？答案是：有！早在1892年 Pick 就談論過腦子裡 meaning system 的理論架構。只不過 Pick 當時所言，而今已成古調，時下皆不談。後人僅記得他所描述的那一群額葉退化的病患，以致於他在這方面的貢獻，也被人遺忘了。
關於 semantic dementia，遠可溯及 Pick，近則與 Tulving 有關。Tulving 提出了episodic memory 及 semantic memory 的假說，Warrington 採納 Tulving 所言，並且認為她所看到的病人是 semantic memory 受損所致。她的想法，說穿了就只有一句話：曾經滄海，才會難為水。只有見過好東西的人，才知道什麼是精緻。舉例而言，semantic dementia 的病人在語言上會有 anomia 的情況。而 Warrington 認為，病人之所以會講不出物品的名稱，表面上是語言的問題，實際上是因為病患心裡根本不存有該物品的意象。連基本的概念都沒有，病人當然就視若無睹。於是病人看到東西，卻說不出其名稱，這就是 anomia。病人若看到文字，卻不曉得是什麼字，表現上就是對 word comprehension 出了問題。Schwartz，Marin 及 Saffran 曾在 1979 年報告過一位這樣的病人：患者可以朗讀，卻完全不了解自己在唸些什麼，典型的 “唸冊歌”。 Mesulam 提出 Primary Progressive Aphasia (PPA) 這個名詞之後， PPA 可以略分為說話流利及不流利兩大類。其中流利型的 PPA，與 Warrington 或 Pick 所報告的是相同的情況。
我們慣於將病患的認知功能分為 memory, attention, language, executive function, higher sensory perception, praxis 等領域來分析。然而若由 semantic dementia 的病患表現，就能了解這些領域並非完全獨立，彼此之間是相關的。名為 semantic memory 的問題，然而患者表現包括 aphasia 及 agnosia。Semantic dementia 病人的表現，令我連想到朱迺欣教授的一段話：如果負責語言功能的 Broca area，並不是像教科書所說，具有固定的部位，那麼所謂的 “左腦語言中樞說” 還會有意義嗎？
大哉斯言。
2010年1月2日 星期六
Is rt-PA indicated?
Suppose you meet with this patient, what will you do?
This 43-year-old lady has hypertension and DM about 5-6 years without medical treatment. This time, she came to our ER because she felt dizzy and facial flushing. Initially at ER, high blood pressure( 270/134mmHg) was found. Besides, hypokalemia(K= 3.3 meq/L) and hyperglycermia(325mg/dl) were also noted. There was no headache, blurred vision, or neurological focal sign. She was treated as hypertensive crisis. After NTG injection, she was transferred to ICU at 17:55. Unfortunately, left limbs weakness and slurred speech occurred about 18:20 PM. At that time, blood pressure was lowered to 95/60 mmHg. NTG was stopped immediately. Left hemiparesis, hypothesia, dysarthria, dysphagia, left central type facial and dizziness persisted. Neurologist was called to see this lady at 19:00. Head CT was normal and NIHSS score was 7. Her brother hesitated thrombolytic therapy for fear of the risk of intracranial bleeding. Emergent brain MRI was therefore done at 20:00, and it revealed acute infarction on right pons and no stenosis of basilar artery. According to her clinical presentation and neuroimaging findings, will you prescribe rt-PA to treat her stroke?
This 43-year-old lady has hypertension and DM about 5-6 years without medical treatment. This time, she came to our ER because she felt dizzy and facial flushing. Initially at ER, high blood pressure( 270/134mmHg) was found. Besides, hypokalemia(K= 3.3 meq/L) and hyperglycermia(325mg/dl) were also noted. There was no headache, blurred vision, or neurological focal sign. She was treated as hypertensive crisis. After NTG injection, she was transferred to ICU at 17:55. Unfortunately, left limbs weakness and slurred speech occurred about 18:20 PM. At that time, blood pressure was lowered to 95/60 mmHg. NTG was stopped immediately. Left hemiparesis, hypothesia, dysarthria, dysphagia, left central type facial and dizziness persisted. Neurologist was called to see this lady at 19:00. Head CT was normal and NIHSS score was 7. Her brother hesitated thrombolytic therapy for fear of the risk of intracranial bleeding. Emergent brain MRI was therefore done at 20:00, and it revealed acute infarction on right pons and no stenosis of basilar artery. According to her clinical presentation and neuroimaging findings, will you prescribe rt-PA to treat her stroke?
2009年5月22日 星期五
2009年4月3日 星期五
Clock Drawing
這位病人於其左額葉有個5公分大的meningioma。我請他畫個三點半的時鐘，病人先是在中央畫個小圈，然後轉著紙寫數字。從1寫到12之後又猶豫許久，經提示，才將時針畫在3-4之間。而分針，他就畫不下去了。
2009年3月20日 星期五
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這位病人於其左額葉有個5公分大的meningioma。我請他畫個三點半的時鐘，病人先是在中央畫個小圈，然後轉著紙寫數字。從1寫到12之後又猶豫許久，經提示，才將時針畫在3-4之間。而分針，他就畫不下去了。 -
Primary progressive aphasia (PPA) 這個名詞是由Mesulam所提出來的。Mesulam在2007年底寫過一篇文章，回溯PPA的發現及發展的經過。故事得要從1975年說起。當時Norman Geschwind離開Boston City Hospit...
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「眾裏尋他千百度， 驀然回首， 那人卻在燈火闌珊處。」 您要不要試試， 以Neurology的觀點， 分析一下這詞所涉及的cortical function?