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.

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.

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.

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.

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

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。

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。