Paste your eDementia with Lewy bodies presenting as probable epileptic seizure
We discuss the case of an 83-year-old man admitted to hospital after losing control of his vehicle due to unexplained altered consciousness. This occurred on a background of multiple similar episodes associated with acutely worsened confusion, superimposed on a gradual cognitive decline spanning 6 years. Organic aetiologies for delirium were excluded and CT and MRI imaging of the brain were negative for cerebrovascular accidents or other epileptiform foci. EEG was negative for epileptiform activity. A diagnosis of seizure in the setting of dementia with Lewy bodies (DLB) was considered. Subsequent brain SPECT and FDG-PET studies supported the diagnosis of DLB. Acute changes in consciousness or cognitive ability are often associated with strokes and seizures in the elderly. However, as illustrated in this case, it is important to consider comorbidities that may occur in the older person.
Epileptic seizures are common in the older population. Many instances of loss of consciousness associated with motor disturbances or other cognitive changes in the elderly are therefore assumed to represent seizure activity. The increased incidence of seizures in the elderly possibly results from alterations in inhibitory-excitatory systems arising from complex neurodegenerative processes that occur in the ageing brain. This includes processes such as Alzheimer disease (AD), dementia with Lewy bodies (DLB) and vascular dementia. Unlike AD and vascular dementia, DLB is not known to be associated with epileptic seizures. Our case illustrates the importance of comprehensive assessment and broad consideration of associated differential diagnoses so that the possibility of DLB is not missed.
An 83-year-old Caucasian male presented to an acute tertiary hospital in Melbourne, Australia, following a motor vehicle accident associated with a period of altered consciousness and subsequent confusion. This admission occurred on a background of multiple similar episodes of confusion over the past 6 months with gradual, superimposed cognitive decline noted for 6 years.
Other than recalling twitching of his right arm on the morning of the accident, he was unable to recall the accident itself or other events in the day leading up to it. He did not acquire any significant head or other injuries and denied associated cardiac or neurological symptoms, including incontinence or tongue biting.
Throughout the acute admission, the patient experienced ongoing fluctuating confusion with one episode of nocturnal absconding to his home. Upon return to the ward, after searching and police involvement, he was unable to account for or recall his behaviour.
On further questioning, his family described six-year history of slow decline in memory. Safety at home has been an increasing concern as he was living alone and has forgotten to turn off the stove a few times. There has also been associated intermittent disorientation, confusion and vagueness which seemed to be preceded by brief lip smacking movements and right arm twitching. These episodes usually happen sporadically with months between each episode but have been increasing in frequency particularly in the last 6 months.
His only past medical history was hypertension, without significant past history of seizures, childhood infections, head trauma or issues at birth, drug intake or cigarettes smoking. He drinks one standard drink per night. Family history was unremarkable for any psychiatric, autoimmune or neurologic conditions.
On examination, he was orientated to place and time. There are no features of Parkinsonism or any focal neurological deficits. The rest of his physical examination was unremarkable. A neuropsychology assessment showed clear cognitive impairment for his age, most markedly in the areas of new learning & memory, attention and visuoconstruction (see Table). Standardised Mini-Mental State Examination score was 26/30 (1/3 for 3-item delayed recall)8. A Cognistat test revealed 17/26 language, 0/6 construction, 1/12 memory, 4/4 calculation, 3/14 reasoning.
Laboratory investigations demonstrated a mild normocytic anaemia (Hb-126, MCV- 88) and mild renal impairment (Urea-6.9, Cr- 81, eGFR-77). Syphilis serology was negative, vitamin B12 was borderline low at 153 (normal 156-698) and HbA1c was 5.3%.
CT followed by MRI Brain showed no evidence of focal atrophy, acute or previous stroke or other abnormalities. EEG demonstrated no activity of an epileptiform or encephalopathic activity.
A diagnosis of partial seizure was made. Levetiracetam was commenced at a dose of 250mg orally twice daily.
Following multidisciplinary assessment and rehabilitation on a subacute ward, the patient was discharged home with supports including personal care, domestic and shopping assistance, meal delivery and medication supervision. There were no seizure-like activities witnessed during the entire three-week inpatient stay.
He was referred for outpatient Neurology review and was advised not to return to driving for a period of at least twelve months (with driving assessment thereafter if seizure-free).
The patient was reviewed as an outpatient at the epilepsy clinic two months later where he described no further loss of consciousness or twitching movements, as well as complete resolution of visual hallucinations.
An outpatient brain SPECT performed four months after showed moderate hypo-perfusion in bilateral occipital lobes with minimal reduction in the posterior cingulate. Hypo-perfusion in the anterior cingulate and right medial frontal lobe was also noted. FDG-PET study showed significant reduction in metabolism in bilateral occipital, parietal and posterior temporal lobes in comparison to a normal subject database. Overall, these findings were suggestive of Lewy body disease.
A repeat neuropsychology assessment was performed at 10 months, which showed further decline of visuospatial skills, visuospatial construction and executive functions (see Table). This cognitive impairment profile, in addition to his clinical history of marked attentional fluctuations and visual hallucinations, is in keeping with a diagnosis of dementia with Lewy bodies.
This case illustrates a diagnostic dilemma where a patient presents with visual hallucinations and automatism which responded well to anti-epileptic therapy, despite having a neuropsychology assessment and brain imaging suggestive of underlying Lewy Body Disease. Are these symptoms explainable by DLB, or does a response to anti-epileptic therapy suggest a diagnosis of seizures? Or is there an association between seizures and underlying neurodegenerative disease such as DLB?
A significant proportion of new onset seizures occur in individuals over the age of 65 years. A seizure diagnosis has significant quality of life implications in older patients, who are already vulnerable to loss of independence, driving restrictions, impaired self-confidence, and risk of falls. Treatment decisions can be complex in older patients, who have increased susceptibility to side effects and an increased likelihood of multiple medical comorbidities.
In adult, the incidence and prevalence of epilepsy is highest in patients over 65 years. Acute symptomatic seizures are provoked events that are not expected to recur in the absence of a particular trigger (eg, hypoglycemia, alcohol withdrawal). Epilepsy is a condition in which recurrent unprovoked seizures are expected in the absence of treatment. Both acute symptomatic seizures and epilepsy occur as a consequence of diseases and conditions that more commonly affect older adults’. Compared with healthy individuals of the same age, patients with Alzheimer disease (AD) have a 6- to 10-fold increased risk of developing clinical seizures during the course of their illness. In a follow-up study with a nested case-control analysis using the United Kingdom-based General Practice Research Database (GPRD), seizures or epilepsy were substantially more common in patients with AD and Vascular dementia (VD) than in dementia-free patients6.
A diagnosis of DLB was made in this case based on presence of severe impairment visuospatial and visuoconstructional ability and a severe executive dysfunction, with the latter characterised by considerable difficulties with cognitive flexibility, inhibition of an autonomic response, planning and organisation, and sematic lexical retrieval. There is also marked impairment in new learning and memory, particularly in the verbal domain. This diagnosis was further supported by functional neuroimaging of the brain.
DLB is increasingly acknowledged as the second most common cause of neurodegenerative dementia after AD. In addition to a decline in mental ability severe enough to interfere with everyday functioning, distinct clinical features of DLB include visual hallucinations, parkinsonism, fluctuation in cognition, dysautonomia, sleep disorders and neuroleptic sensitivity.
Our patient presented with periods of altered consciousness and confusion associated with lip smacking and arm twitching, symptoms suggestive of seiziues documented response to anticonvulsants. However, he also had significant visuospatial and visuoconstructional impairment and recurrent complex visual hallucination, with a brain SPECT suggestive of underlying DLB. It is difficult to determine whether the visual hallucinations, which responded to antiepileptic therapy, are related to seizures or DLB. Additionally, the presence of 2 distinct diagnosis in this patient raises the possibility that they may be an association between them.
We postulate that DLB could potentially predispose a person to seizures, similar to that seen in other neurodegenerative disorder such as AD or VD. Our postulation was supported by similar case report of patient with DLB presenting with focal myoclonic jerks and rare EEG findings. Conversely a patient with epileptic seizure presents with symptoms that mimic DLB such as vivid recurrent visual hallucination associated with fluctuating cognition.
Clinical diagnostic criteria for DLB were first published in 1995. These criteria were revised in 2005 when DLB was proposed as an entity including Parkinson’s disease with dementia and DLB with central features, core features, suggestive features, supportive features, features of DLB diagnosis is less likely and temporal sequence of symptoms (Appendix 1). Among these features, seizures or seizure-like activity were not included apart from “transient, unexplained loss of consciousness†as supportive features for diagnosis.
However, in case report of Park et al, clinicians noticed epileptic seizures may cause symptoms that mimic DLB such as vivid recurrent visual hallucination associated with fluctuating cognition. On the other hand, the case presentation of Sun et al described atypical manifestation and rare EEG findings in patient with Lewy body dementia. To add, a case report by Ukai et al discusses whether Lewy body disease might cause transient epileptic amnesia ( TEA ). The postulation of DLB could potentially predispose a person to seizures, similar to that seen in other neurodegenerative disorder such as AD or VD was raised. A larger cohort of patients will be needed to test this hypothesis
In summary, this case demonstrates that careful and detailed history taking is required in elderly patients presented with new onset seizures to exclude common causes as well as not uncommon causes of neurodegenerative disorders including Alzheimer’s disease, Parkinson disease with dementia and Lewy Body Disease.
1. Epileptic seizures are common in the older population, probably as a consequence of complex neurodegenerative process occurring with ageing.
2. While many instances of loss of consciousness associated with motor disturbances or other cognitive changes in older people may represent seizure activity, a comprehensive assessment considering a broad range of differential diagnoses is required.
3. The history and response to anticonvulsant therapy in our patient’s case are suggestive that he was suffering from epileptic seizures which are not well (or have not previously?) described as having an association with DLB.
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