Epilepsy and prion diseases: A narrative review.

Epileptic seizures have been described as one feature of prion diseases, but are an unusual clinical presentation. The aim of this narrative Review was to summarize current knowledge of epileptic seizures in the various forms of prion diseases, from a clinical perspective. Examination of the published literature identified no systematic studies; the evidence base is largely anecdotal, consisting mainly of case studies and small case series. Hence, uncertainty prevails as to seizure frequency, semiology, treatment, and pathogenesis in prion diseases. Seizures probably occur in around 10% of sporadic cases but less frequently in iatrogenic and familial forms, with the possible exception of the E200K mutation. The literature suggests a predominance of focal motor and nonconvulsive status epilepticus. Electroencephalographic accompaniments include periodic lateralized or generalized periodic epileptiform discharges (PLEDs, GPEDs), sometimes predating the more typical periodic sharp wave complexes. There are no convincing accounts of successful antiepileptic drug therapy. The underlying mechanisms of epileptogenesis in prion diseases may include loss of cellular prion protein function (PrPc) and aggregation of abnormally folded prion protein (PrPSc). The need for systematic studies and clinical trials to expand the evidence base surrounding epilepsy and prion diseases is evident.

The overlap between epilepsy and Alzheimer's disease and the consequences for treatment.

Introduction: Alzheimer's disease may be associated with both clinical and subclinical epileptic seizure activity. Once regarded as an epiphenomenon, epileptiform activity may, in fact, be an integral part of the Alzheimer's phenotype, and may be not only a symptomatic therapeutic target but also a possible mechanism to retard or prevent disease progression. Areas covered: The authors review clinical research articles with a focus on the semiology, epidemiology, and treatment of seizures in Alzheimer's disease, and also look at some experimental animal model studies which have informed clinical thinking on seizure aetiopathogenesis. The evidence base for treatment decisions is sparse. A brief overview of the clinical assessment of Alzheimer's disease patients considering relevant differential diagnoses and diagnostic pitfalls is presented. Expert opinion: Studies of epileptic seizures in Alzheimer's disease have become more frequent over the last 5-10 years. Understanding of seizure semiology, epidemiology, and possible pathogenesis has increased. However, the optimal management of seizures in this context remains unknown, largely due to the paucity of studies sufficient to examine this question. Clearly, such studies will be required, not only to inform clinicians about symptomatic control of seizures in Alzheimer's disease but also to investigate whether this might impact on disease progression.

Codex (Cognitive Disorders Examination) Decision Tree Modified for the Detection of Dementia and MCI.

Many cognitive screening instruments are available to assess patients with cognitive symptoms in whom a diagnosis of dementia or mild cognitive impairment is being considered. Most are quantitative scales with specified cut-off values. In contrast, the cognitive disorders examination or Codex is a two-step decision tree which incorporates components from the Mini-Mental State Examination (MMSE) (three word recall, spatial orientation) along with a simplified clock drawing test to produce categorical outcomes defining the probability of dementia diagnosis and, by implication, directing clinician response (reassurance, monitoring, further investigation, immediate treatment). Codex has been shown to have high sensitivity and specificity for dementia diagnosis but is less sensitive for the diagnosis of mild cognitive impairment (MCI). We examined minor modifications to the Codex decision tree to try to improve its sensitivity for the diagnosis of MCI, based on data extracted from studies of two other cognitive screening instruments, the Montreal Cognitive Assessment and Free-Cog, which are more stringent than MMSE in their tests of delayed recall. Neither modification proved of diagnostic value for mild cognitive impairment. Possible explanations for this failure are considered.

Facial Onset Sensory and Motor Neuronopathy: Further Evidence for a TDP-43 Proteinopathy.

Three patients with the clinical and investigation features of facial onset sensory and motor neuronopathy (FOSMN) syndrome are presented, one of whom came to a post-mortem examination. This showed TDP-43-positive inclusions in the bulbar and spinal motor neurones as well as in the trigeminal nerve nuclei, consistent with a neurodegenerative pathogenesis. These data support the idea that at least some FOSMN cases fall within the spectrum of the TDP-43 proteinopathies, and represent a focal form of this pathology.

Herpes simplex virus encephalitis in pregnancy - a case report and review of reported patients in the literature.

BACKGROUND: Herpes simplex virus (HSV) encephalitis is the most common sporadic cause of encephalitis with significant morbidity and mortality that is drastically reduced by early antiviral treatment. CASE PRESENTATION: We report a 37 year old woman, 33 weeks pregnant, who presented with seizures due to proven HSV-1 encephalitis, and who had had a previous episode of probable viral encephalitis aged 14 years. She was successfully treated with aciclovir on both occasions and, in the latter, went on to deliver a healthy infant. This case is compared with 17 cases of HSV encephalitis in pregnancy in the literature identifying a predominance in the late 2nd and 3rd trimesters, perhaps in part due to immunological changes in pregnancy. The clinical presentation is also compared with non-pregnant patients with HSV encephalitis in the largest prospective UK and European studies. We also present practical advice on management from recent national guidelines. CONCLUSION: When pregnant women present with new seizures, headache, impaired consciousness or altered behaviour urgent investigation is required to identify common diagnoses, such as eclampsia, venous sinus thrombosis and metabolic disturbances. Nevertheless, viral encephalitis is a very treatable cause of this presentation with potentially serious complications if missed, and may be more common in latter stages of pregnancy. Encephalitis should not be discounted if the patient is afebrile, has a normal Glasgow coma score, or the cerebrospinal fluid white cell count is only slightly elevated, as these features are well recognised in viral encephalitis.