L-2-Hydroxyglutaric aciduria presenting with severe autistic features

L-2-Hydroxyglutaric aciduria (L-2-HGA) is an autosomal recessive neurometabolic disorder characterized by psychomotor delay, ataxia, macrocephaly and typical neuroradiological findings of subcortical leucoencephalopathy. Recently, the disease causing gene has been discovered (L2HGDH) encoding L-2-hydroxyglutarate dehydrogenase. We present a 3-year-old boy with L-2-HGA, who demonstrated macrocephaly, noted already in utero with ultrasound. Cranial MRI demonstrated diffuse subcortical encephalopathy with increased signal of the subcortical white matter. Subsequent metabolic screening revealed increased levels of L-2-HGA, and genomic DNA analysis demonstrated two missense mutations in L-2-HGDG. Patient's further motor development was mildly impaired, whilst his speech development was profoundly impaired (first words at the age of 2 years). Since the age of 2 years he started demonstrating autistic repetitive behaviors and movements, increasing aloofness to his environment and limitations in the variety of spontaneous activity (CARS score: 44/60-severe autism). Autism has not so far been described in L-2-HGA and may be considered as an additional feature of the phenotypic spectrum.     

Hemiconvulsion-hemiplegia-epilepsy syndrome as a presenting feature of L-2-hydroxyglutaric aciduria

L-2-hydroxyglutaric aciduria was diagnosed in a 9-month-old female infant after a complex febrile convulsion with subsequent transient left-sided hemiplegia. The symptoms were consistent with acute hemiconvulsion-hemiplegia-epilepsy syndrome. Magnetic resonance imaging (MRI) of the brain revealed distinct white-matter abnormalities in the bifrontal and bioccipital periventricular area and increased signal intensity in the lenticular, caudate, and dentate nuclei, consistent with L-2-hydroxyglutaric aciduria. Increased concentrations of L-2-hydroxyglutaric acid were detected in the urine, plasma, and cerebrospinal fluid. The patient was homozyous for the p.Lys81Glu (c.241A>G) missense mutation in the L-2-HGA gene, confirming the diagnosis of L-2-hydroxyglutaric aciduria. Acute hemiconvulsion-hemiplegia-epilepsy syndrome has not been reported as a presenting feature in L-2-hydroxyglutaric aciduria. In patients with prolonged or complicated febrile seizures such as hemiconvulsion-hemiplegia-epilepsy syndrome, L-2-hydroxyglutaric aciduria should be included in the differential diagnosis, especially in children with concomitant macrocephaly.     

Tonic status epilepticus presenting as confusional state

A 17-year-old epileptic was admitted to the hospital in a confused state. Electroencephalography (EEG) with polygraphic recording revealed tonic status epilepticus. Therapy with phenytoin, phenobarbital, valproic acid, and methyl phenidate was unsuccessful. Intravenous diazepam exacerbated the seizures. EEG with polygraphic recording may detect clinically inapparent tonic seizures in epileptics with unexplained confusion, and when generalized paroxysmal fast activity occurs during EEG recording.     

De-novo simple partial status epilepticus presenting as Wernicke's aphasia

Language disturbances manifesting as brief periods of speech arrest occur with seizures originating in the frontal or temporal lobes. These language disturbances are usually present with other features of seizures or may occur in an episodic fashion suggesting their likely epileptic origin. Sustained but reversible aphasia as the sole manifestation of partial status epilepticus is rare, particularly without a history of prior seizures. A few cases have been described in the literature where Broca's or mixed aphasia seems to be more common than Wernicke's aphasia. Here we describe a patient who presented with Wernicke's aphasia secondary to simple partial status epilepticus but without any other features of seizures. The diagnosis was confirmed on EEG and the aphasia reversed after antiepileptic treatment.     

Novel neurofibromatosis type 2 mutation presenting with status epilepticus

Neurofibromatosis type 2 (NF2) is a dominantly inherited syndrome caused by mutations of the tumour‐suppressor NF2, which encodes the merlin protein. Mutations are associated with a predisposition to development of benign tumours in the central nervous system. Even though cerebral cortical lesions are frequently associated with seizures, epilepsy is rarely described in NF2. Here, we describe an adult case of NF2 in which the onset of symptoms was characterised by status epilepticus. In this patient, we identified the novel c.428_430delCTTdel mutation in NF2, involving the amino‐terminal FERM domain, which is fundamental for the correct tumour suppressor function of the protein. Bioinformatic analyses revealed an important structural perturbation of the FERM domain, with a predicted impairment of the anti‐tumour activity.     

Nonconvulsive status epilepticus presenting as a subacute progressive aphasia.

We report a 62-year-old man with non-convulsive status epilepticus (NCSE) presenting as a progressive aphasia that developed insidiously over 5 weeks. On video-EEG monitoring, aggravation of the aphasia coincided with occurrence of seizure activities arising from the left fronto-temporal area. Brain MRI was noncontributory but a fluorodeoxyglucose-PET scan revealed a hypometabolism in the left anterior temporal area. Following anticonvulsant treatment, aphasia recovered gradually over several weeks despite prompt resolution of epileptic discharges on EEG. Our patient's findings, gradual onset of isolated aphasia with gradual resolution after initiation of treatment, may differ from previously reported cases with aphasic status epilepticus because their aphasia showed abrupt onset and rapid resolution with anticonvulsant medication.     

Neurosyphilis presenting with status epilepticus.

Three patients with neurosyphilis are reported. The first and third patients presented with convulsive status epilepticus and the second with non-convulsive status after penicillin administration. In all cerebrospinal fluid and the serum Venereal Disease Research Laboratory Test (VDRL) and Treponema Pallidum hemagglutination (TPHA) or fluorescent treponemal antibody absorption test (FTA-ABS) were positive, but HIV serology was negative. Their EEGs showed periodic, lateralized, epileptiform discharges (PLEDs) just after SE. The first and third patients had no history of epilepsy. Seizures started as focal motor attacks but then secondarily generalized. The first patient's cranial MRI showed cerebral atrophy and hyperintensity involving bilateral medial and anterior temporal regions, more prominent on the left and which disappeared after penicillin treatment. The second case, after receiving penicillin, had nonconvulsive SE, a clinical presentation suggesting a Jarisch-Herxheimer reaction (JHR). Her cranial MR revealed moderate cortical atrophy and widespread confluent hyperintense foci mainly in both periventricular areas, corona radiata and centrum semiovale. MRI of the third case showed a large, left sylvian, arachnoid cyst without mass effect. Executive dysfunction was observed in follow-up neuropsychological tests in all patients. When investigating status epilepticus, neurosyphilis as a cause must not be forgotten.     

A novel mutation as a cause of L-2-hydroxyglutaric aciduria

Journal of Neurology -     

Creutzfeldt-Jakob disease presenting as hyperparathyroidism and generalized tonic status epilepticus.

Creutzfeldt-Jakob disease is the most common disorder among the very rare human transmissible subacute spongiform encephalopathies. Sporadic, familial or iatrogenic forms of the disease can be seen. The common presentations of the disease include rapidly progressive cognitive decline, behavioral changes, visual disturbances and cerebellar dysfunction. Hyperparathyroidism and toxicity of lithium and bismuth have been reported to induce similar symptoms and EEG findings, leading to a Creutzfeldt-Jakob like syndrome. We report a very rare case of Creutzfeldt-Jakob disease presenting with hyperparathyroidism and generalized tonic status epilepticus.     

De novo aphasic status epilepticus as presenting symptom of multiple sclerosis

Journal of Neurology -