Late onset AMACR deficiency with metabolic stroke-like episodes and seizures.

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal disorder causing pristanic acid accumulation. Only 16 cases have been described so far. A female in her seventh decade presented with episodes of dysphasia, headache and sensory disturbance inconsistent with migraine, epilepsy or transient ischaemic attack. An MRI demonstrated unusual changes in the pons, red nuclei, thalami and white matter. Mitochondrial disease was suspected but detailed testing was negative. After eight years of symptoms, she developed a febrile encephalopathy with hemispheric dysfunction, focal convulsive seizures and coma. Her condition stabilised after one month. Lacosamide was continued for seizure prevention. The diagnosis remained elusive until whole genome sequencing revealed AMACR deficiency. Pristanic acid levels were highly elevated and dietary modification was recommended. Genetic peroxisomal disorders can present in older age; our patient is the oldest in the AMACR deficiency literature. Novel features in our case include central apnoea, dystonia and rapid eye movement behaviour disorder.

Lemierre's syndrome.

Lemierre's syndrome is a rare and potentially life-threatening condition that follows an oropharyngeal infection, typically from Fusobacterium necrophorum, and usually affects healthy adolescents or young adults. The characteristic features are septic thrombophlebitis of the internal jugular vein and septic embolism leading to multiorgan involvement, commonly the brain, lungs and bones. We report a man with presenting symptoms suggesting hemicrania continua, whose initial imaging showed no features of dural venous sinus or jugular thrombosis. Two weeks later, he had fever, sore throat, cervical lymphadenopathy and Actinomyces meyeri grew from peripheral blood cultures. Further imaging identified thrombosis of the internal jugular vein and cerebral venous sinuses, with multifocal cavitating lung lesions. Following antibiotics and anticoagulation, he recovered without residual deficits. Lemierre's syndrome when recognised and treated early has a good prognosis but delayed treatment may result in significant morbidity or mortality.

Acute neurological consequences of novel psychoactive substance use: a retrospective review in a large UK hospital.

BACKGROUND: Novel psychoactive substances (NPS) are a growing public health concern. We aimed to identify the acute neurological consequences of NPS. METHOD: We performed a retrospective case-note review of patients who presented to the emergency department after taking NPS. RESULTS: We identified 237 admissions from 190 patients, mostly young men. There were high rates of psychiatric comorbidity (43%), unemployment (39%), homelessness (24%) and incarceration (17%). Most reported use of synthetic cannabinoids (SC; 91%). Some took synthetic cathinones (SCath; 7%) or nitrous oxide (NOS; 2%). SC caused impaired consciousness (61%) and seizures (16%). SCath users presented with psychiatric disturbance or seizures (55%). Most patients were managed conservatively (67%) and a small proportion (14%) were referred to drug or psychology services. CONCLUSIONS: NPS users represent a vulnerable group in society. Certain clinical features may suggest the type of NPS used. Most patients require supportive management and onward referral to drug addiction services is recommended.

Is NIPA1-associated hereditary spastic paraplegia always 'pure'? Further evidence of motor neurone disease and epilepsy as rare manifestations.

Pathogenic variants in the nonimprinted in Prader-Willi/Angelman syndrome (NIPA1) gene typically present with pure hereditary spastic paraplegia (HSP) but complex cases are described. We present a patient with childhood idiopathic generalised epilepsy (IGE) who later developed HSP. She rapidly deteriorated 27 years later with clinically definite amyotrophic lateral sclerosis (ALS). Her family history included HSP, IGE and motor neurone disease. Genetic testing identified a pathogenic variant in the NIPA1 gene associated with spastic paraplegia 6 (SPG6). This case provides the first description of NIPA1 in a family with epilepsy, ALS and thus complex HSP.

The prescribable drugs with efficacy in experimental epilepsies (PDE3) database for drug repurposing research in epilepsy.

OBJECTIVE: Current antiepileptic drugs (AEDs) have several shortcomings. For example, they fail to control seizures in 30% of patients. Hence, there is a need to identify new AEDs. Drug repurposing is the discovery of new indications for approved drugs. This drug "recycling" offers the potential of significant savings in the time and cost of drug development. Many drugs licensed for other indications exhibit antiepileptic efficacy in animal models. Our aim was to create a database of "prescribable" drugs, approved for other conditions, with published evidence of efficacy in animal models of epilepsy, and to collate data that would assist in choosing the most promising candidates for drug repurposing. METHODS: The database was created by the following: (1) computational literature-mining using novel software that identifies Medline abstracts containing the name of a prescribable drug, a rodent model of epilepsy, and a phrase indicating seizure reduction; then (2) crowdsourced manual curation of the identified abstracts. RESULTS: The final database includes 173 drugs and 500 abstracts. It is made freely available at www.liverpool.ac.uk/D3RE/PDE3. The database is reliable: 94% of the included drugs have corroborative evidence of efficacy in animal models (for example, evidence from multiple independent studies). The database includes many drugs that are appealing candidates for repurposing, as they are widely accepted by prescribers and patients-the database includes half of the 20 most commonly prescribed drugs in England-and they target many proteins involved in epilepsy but not targeted by current AEDs. It is important to note that the drugs are of potential relevance to human epilepsy-the database is highly enriched with drugs that target proteins of known causal human epilepsy genes (Fisher's exact test P-value < 3 × 10-5 ). We present data to help prioritize the most promising candidates for repurposing from the database. SIGNIFICANCE: The PDE3 database is an important new resource for drug repurposing research in epilepsy.

The impact of epilepsy on the quality of life of patients with meningioma: A systematic review.

Quality of life (QoL) is regarded as an important outcome measure in meningioma, and studies have investigated the role of various clinical and demographic factors. Epilepsy is known to impair quality of life but the impact of epilepsy on quality of life in a meningioma population is not well defined. The aim of this systematic review is to identify and summarise the current literature on meningioma, epilepsy and quality of life. A PubMed search was performed that identified 162 articles. Only 4 articles relevant to meningioma, epilepsy and QoL were found and each were analysed in terms of design, data, findings and conclusions. Each article was different in terms of study population, aims and outcome measure, but all suggest that epilepsy has an impact on quality of life. Anti-epileptic drugs, uncontrolled seizures and cognitive dysfunction may be particularly significant. The identified articles were weakened by small sample size, short follow-up, a lack of recorded epilepsy variables and the use of quality of life measures that are either too specific or not validated. Future studies are warranted to improve understanding in this topic, aid clinical decisions and improve QoL in these patients.