Saif Razvi

Newly presenting psychogenic nonepileptic seizures: incidence, population characteristics, and early outcome from a prospective audit of a first seizure clinic.

There are few published population-based data for psychogenic nonepileptic seizures (PNES). We prospectively identified first presentations of PNES from a population of 367,566, over 3 years. PNES were diagnosed in 68 patients, in 54 of whom the diagnosis was confirmed by video/EEG recording, indicating an incidence of 4.90/100,000/year. Median diagnostic delay was 0.6 ± 0.2 year. At presentation with PNES, our patients already had high rates of psychological morbidity, medically unexplained symptoms other than PNES, and economic dependence. At 3 months postdiagnosis, 27 of 54 patients (50.0%) were spell free. For 24 of the 27 patients (88.9%), spells ceased immediately on communication of the diagnosis. At 6 months, 24 of 54 patients (44.4%) were spell free. Poor early outcome was predicted by unemployment. Our data suggest that early outcome is good in patients with recent-onset PNES, but some patients relapse quickly.

The prevalence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the west of Scotland

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is caused by mutations of the Notch3 gene on 19p13. Varying phenotypic expression leads to under recognition and misdiagnosis. Prevalence therefore remains uncertain. We sought to estimate the prevalence of CADASIL in the west of Scotland. Methods: A register for CADASIL was established at a regional neurosciences centre in 2002. All patients with genetically (exons 3, 4, 5, and 6) or histologically confirmed CADASIL residing in two defined administrative health areas were identified. Pedigree members at varying risk of carrying the mutation were also identified and the number of probable Notch3 mutation carriers in the defined population was predicted. Prevalence was calculated for definite CADASIL cases, with and without probable carrier numbers, based upon adult population figures from the 2002 national census. Results: Twenty two individuals from seven pedigrees with confirmed CADASIL and resident in the defined geographical area were identified, yielding a prevalence of 1.98 (95% confidence interval 1.24–3.00) per 100 000 adults. An additional 37 individuals were predicted to be carriers of the Notch3 mutation, yielding a probable mutation prevalence of 4.14 (3.04–5.53) per 100 000 adults. Conclusions: The prevalence of genetically proven CADASIL was 1.98 per 100 000 adults in the defined population. This figure underestimates disease burden.

Newly diagnosed psychogenic nonepileptic seizures: Health care demand prior to and following diagnosis at a first seizure clinic

Patients with psychogenic nonepileptic seizures (PNES) are heavy users of emergency and nonemergency health care. We performed a 1-year prospective audit of use of a group of PNES-related health care items in patients with newly diagnosed (mean duration: 7.3 months) PNES from PNES onset to diagnosis and from diagnosis to 6 months postdiagnosis. Twenty-eight patients (20 women, age: 34±16 years) were responsible for 14 general practitioner home visits, 31 ambulance calls, 34 emergency department visits, 21 hospital admissions (66 inpatient days), 8 MRI scans, 24 CT scans, 2 standard EEGs, 28 short video EEG recordings, and 5 ambulatory EEG recordings. In the 6 months following diagnosis, there were 2 emergency department visits (94.1% reduction), no hospital admissions (100% reduction), 2 ambulance calls, no general practitioner visits, 1 MRI scan, and no CT scans or EEGs. The immediacy of this marked health care demand reduction suggests that the relationship between presentation of diagnosis and health care demand reduction is causal.

Single gene disorders causing ischaemic stroke

Stroke is the third most common cause of death and the leading cause of long-term neurological disability in the world. Conventional vascular risk factors for stroke contribute approximately to only forty to fifty percent of stroke risk. Genetic factors may therefore contribute to a significant proportion of stroke and may be polygenic, monogenic or multi-factorial. Monogenic (single gene) disorders may potentially account for approximately one percent of all ischaemic stroke. Monogenic stroke disorders include conditions such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) and hereditary endotheliopathy, retinopathy, nephropathy and stroke (HERNS). In addition, other monogenic conditions such as sickle cell and Fabry disease also lead to stroke. These monogenic disorders cause either small vessel or large vessel stroke (or a combination of both) and serve as useful models for understanding and studying conventional stroke and cerebrovascular disease and its accompaniments such as vascular dementia.

Accelerated long-term forgetting in temporal lobe epilepsy: Verbal, nonverbal and autobiographical memory

Patients with temporal lobe epilepsy (TLE) often present with memory complaints despite performing within normal limits on standard memory tests. One possible explanation for this phenomenon is accelerated long-term forgetting (ALF). The present study investigated material-specific ALF in patients with unilateral TLE and also examined whether ALF could be demonstrated on a novel, standardized anterograde autobiographical memory (ABM) task. Fourteen patients with TLE and 17 controls were administered verbal, nonverbal and ABM event memory tasks. The participants were tested for immediate recall, recall and recognition at 30-minute delay, and recall and recognition after four weeks. The extent of ALF was calculated based on the percentage decay of memory from the 30-minute delay trial to the four-week delay trial. Patients with left TLE showed significantly greater ALF for verbal material and a trend towards greater forgetting of ABM. Patients with right TLE showed a non-significant trend towards greater ALF for nonverbal material. Patients with unilateral hippocampal abnormalities showed greater ALF compared to patients without hippocampal abnormalities. Patients with seizures that generalize had more global memory deficits and greater ALF. We conclude that patients with unilateral TLE show material-specific ALF, which appears to be more pronounced with an abnormal hippocampus or seizures that secondarily generalize.

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: an important cause of stroke in young people

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes is a progressive, multisystem mitochondrial disease affecting children and young adults. Patients acquire disability through stroke-like episodes and have an increased mortality. Eighty per cent of cases have the mitochondrial mutation m.3243A>G which is linked to respiratory transport chain dysfunction and oxidative stress in energy demanding organs, particularly muscle and brain. It typically presents with seizures, headaches and acute neurological deficits mimicking stroke. It is an important differential in patients presenting with stroke, seizures, or suspected central nervous system infection or vasculitis. Investigations should exclude other aetiologies and include neuroimaging and cerebrospinal fluid analysis. Mutation analysis can be performed on urine samples. There is no high quality evidence to support the use of any of the agents reported in small studies. This article summarises the core clinical, biochemical, radiological and genetic features and discusses the evidence for a number of potential therapies.

Changing clinical patterns and increasing prevalence in CADASIL

CADASIL is a monogenic small vessel vasculopathy causing recurrent stroke. Early descriptions suggested dementia and disability were common from the 5th decade but there is evidence of marked phenotypic variability. We investigated the prevalence and clinical features of CADASIL in the west of Scotland.

Is inadequate family history a barrier to diagnosis in CADASIL

Objectives –  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) has typical clinical features that include stroke, migraine, mood disturbances and cognitive decline. However, misdiagnosis is common. We hypothesized that family history is poorly elicited in individuals presenting with features of CADASIL and that enquiry into family history of all four cardinal manifestations of CADASIL is superior to elicitation of family history of premature stroke alone in raising the diagnostic possibility of CADASIL.

Cluster headache due to internal carotid artery dissection

Sirs: Cluster headache is a primary headache disorder characterised by bouts of sudden episodic peri-orbital or fronto-temporal pain lasting 15 to 180 minutes. The headaches are accompanied by at least one or more ipsilateral autonomic disturbances (ptosis, miosis, lacrimation, conjunctival injection, rhinorrhoea, forehead or facial sweating, lid oedema). Cluster headache attacks occur in periods lasting from 7 days to 1 year separated by pain-free periods lasting 1 month or longer. Frequency of attacks may range from one every other day to eight a day. According to the International Classification of Headache Disorders, history, physical examination and investigation must not suggest another disorder [1]. The annual incidence of spontaneous non-traumatic internal carotid artery dissection (ICAD) is estimated to be 2.5 to 3 per 100,000 [5]. Headache is the most common symptom (68–74 %) of non-traumatic ICAD and its most frequent initial symptom (47–58 %) [2, 12]. ICAD headache is ipsilateral to dissection in 79 % of patients, continuous in 73 %, pulsating in 25 % and anterior in location in 60 % [12]. Duration of headache ranges from 1 hour to 30 days with median duration of 3 to 5 days. A painful Horner’s syndrome is found in 31 % of ICAD patients and may be its only manifestation in 16 % [2]. Of patients with ICAD 26 % have neck pain. We report a 44-year-old male who presented with six-week history of recurrent right peri-orbital headache. Headaches were sudden, severe, pulsating, of one to six hour duration and occurred at least thrice a week. Headache was accompanied by ipsilateral ptosis, conjunctival injection, lacrimation and nasal stuffiness. There was no obvious diurnal periodicity. In the first four weeks, ptosis resolved between headaches. In the subsequent two weeks preceding admission, there was subtle residual partial ptosis in between headache attacks. Examination during headache revealed right Horner’s syndrome with partial ptosis and miosis, accompanied by ipsilateral lacrimation, eyelid oedema and conjunctival injection. The remaining cranial nerves (including hypoglossal nerve) and neurological examination were normal. The above features satisfied criteria “A to D” for cluster headache of the International Classification of Headache Disorders (number, site and duration, accompanying symptoms, frequency of headaches) [1]. Criterion E stipulates that other causes for the headache must be ruled out. We therefore performed further investigations. Computed tomographic imaging of the brain was normal. Multi-slice computed tomographic angiography (MDCTA) of the extra-cranial and intra-cranial vasculature was performed. It demonstrated dissection of the right internal carotid artery (Fig. 1). Fat-saturated T1-weighted magnetic resonance imaging of the neck displayed high signal compatible with blood products within the wall of the right internal carotid artery confirming the dissection (Fig. 1). As the patient was fairly distressed by his headache and claustrophobic, standard magnetic resonance imaging of brain was not performed. However, repeat computed tomographic imaging of brain performed one week later did not demonstrate infarction. The patient was anti-coagulated. Sumatriptan was recommended for acute symptomatic relief of headache (reported benefit in ICAD headache as well [7]). Verapamil is recommended as prophylactic therapy for conventional cluster headache [8] and was therefore initiated as prophylactic therapy in our patient, although there is no current literature suggesting its utility in cluster headache due to ICAD. There was complete resolution of headaches over the next two weeks and the patient was entirely asymptomatic at follow-up eight months later. Repeat CTA performed at eight months follow-up demonstrated normal carotid vasculature, without evidence of residual dissection. Verapamil and anticoagulation were withdrawn due to clinical and radiological resolution. Diagnosis of cluster headache according to the International Classification of Headache Disorders is clinical and depends upon assessment and investigation excluding an alternate diagnosis [1]. In routine practice, individuals with cluster headache have diagnosis made upon clinical grounds with structural neuroimaging requested in a substantial proportion. Few patients have carotid imaging. In recent years, individuals with cluster headache secondary to ICAD have been described [10, 11]. Identification of ICAD is important as it has substantial risk of stroke (55 %) with alternate management and prognosis [13]. LETTER TO THE EDITORS

Neurological consultations in the medical intensive care unit

Critical care therapy has advanced over the past two decades, treating more patients and providing more complex care. However, the improved survival from septic shock, adult respiratory distress syndrome (ARDS), and multiple organ system failure results in critically ill patients facing a spectrum of new complications secondary to both illness and treatment. A third of intensive care unit (ICU) admissions have a neurological complication detrimental to outcome.1 Neurological status (mainly depressed consciousness) is the major contributor to prolonged ventilation in a third of those who need it and is a significant factor in an additional 40%. Neurological complications double both the length of stay in hospital and the likelihood of death; the mortality rate for patients with neurological complications is 55% compared to 29% for those without. It is therefore unsurprising that neurologists are being increasingly called upon to review patients on the medical intensive care unit (MICU). A neurological opinion is usually requested: The neurologist must approach these complex patients in a logical, meticulous, and sensitive manner. There are obvious inherent difficulties in reviewing on the MICU: The terminologies used on the ICU are formidable and often ill understood by the consulting clinician. Knowledge of the taxonomy of sepsis and allied syndromes is essential in appreciating their neurological …