Frontal lobe dysfunction in sporadic hyperekplexia--case study and literature review.

Hyperekplexia (HE), or startle disease, is usually a familial disorder associated with mutations in the glycine receptor alpha1 subunit gene (GLRA1), characterised by exaggerated startle reactions to unexpected auditory, somaesthetic and visual stimuli. Non-familial cases may be idiopathic, or associated with pathology usually in the brainstem or rarely in the supratentorial compartment. The pathophysiological basis of HE is unclear. We report the case of a 40-year-old woman presenting with excessive startle response to unexpected stimuli and falls since the age of 16 years. There was no family history. She was initially diagnosed with epilepsy and started on phenytoin with no resolution of her symptoms. Clinical examination revealed hyperreflexia and an insecure broad-based gait but no other abnormalities. Routine comprehensive neuropsychological assessment revealed below average intelligence with signs of frontal lobe dysfunction. EEG showed non-specific abnormalities in the right frontal and central regions. A (99m)Tc-HMPAO SPET scan revealed hypoperfusion in the frontal (worse on the right) and temporal lobes and to a lesser extent in the basal ganglia. MRI was normal, as well as blood and CSF tests. No mutations were found in a genetic analysis of GLRA1. The patient improved partially with treatment by clonazepam. The localisation of the clinical and neuropsychological findings accord with the EEG and SPET scan abnormalities in our patient and corroborates previous reports. Appropriate neuropsychological testing and functional imaging enable more accurate delineation of the clinical phenotype of this rare disorder.

Mitochondrial transfer RNA(Phe) mutation associated with a progressive neurodegenerative disorder characterized by psychiatric disturbance, dementia, and akinesia-rigidity.

BACKGROUND: Mitochondrial diseases are characterized by wide phenotypic and genetic variability, but presentations in adults with akinetic rigidity and hyperkinetic movement disorders are rare. OBJECTIVES: To describe clinically a subject with progressive neurodegeneration characterized by psychosis, dementia, and akinesia-rigidity, and to associate this phenotype with a novel mitochondrial transfer RNA(Phe) (tRNA(Phe)) (MTTF) mutation. DESIGN, SETTING, AND PATIENT: Case description and detailed laboratory investigations of a 57-year-old woman at a university teaching hospital and a specialist mitochondrial diagnostic laboratory. RESULTS: Histopathological findings indicated that an underlying mitochondrial abnormality was responsible for the subject's progressive neurological disorder, with mitochondrial genome sequencing revealing a novel m.586G>A MTTF mutation. CONCLUSIONS: The clinical phenotypes associated with mitochondrial disorders may include akinesia-rigidity and psychosis. Our findings further broaden the spectrum of neurological disease associated with mitochondrial tRNA(Phe) mutations.

A case of voltage-gated potassium channel antibody-related limbic encephalitis.

BACKGROUND: A 56-year-old man presented to hospital with a 6-month history of recurrent episodes of altered behavior and 'odd' episodes. He had become apathetic and uninterested in his family. He had no relevant past medical or family history. General and physical neurological examinations were unremarkable, as was bedside cognitive testing. INVESTIGATIONS: Brain MRI scan, 24-h electroencephalogram, serum and cerebrospinal fluid testing for voltage-gated potassium channel antibodies, blood screening for tumors, CT scans of the chest, abdomen and pelvis, whole-body PET scan, neuropsychological examination, brain 18F-fluorodeoxyglucose-PET scan. DIAGNOSIS: Voltage-gated potassium channel antibody-related limbic encephalitis. MANAGEMENT: Antiepileptic drugs, immunomodulatory therapy, oral steroids, plasma exchange.

Acquired narcolepsy in an acromegalic patient who underwent pituitary irradiation.

The authors report the case of a 60-year-old man with acromegaly, who developed narcolepsy 2 weeks after completing radiotherapy for a pituitary adenoma. Cataplexy and sleepiness were predominant symptoms. Onset of narcolepsy is unusual at this age and the temporal relationship following radiotherapy suggests this treatment was implicated. His CSF hypocretin levels were normal, indicating other factors may be important in his narcolepsy.