How to Detect Isolated PEX10-Related Cerebellar Ataxia?

A 4-year-old boy presented with subacute onset of cerebellar ataxia. Neuroimaging revealed cerebellar atrophy. Metabolic screening tests aiming to detect potentially treatable ataxias showed an increased value (fourfold upper limit of normal) for phytanic acid and elevated very-long-chain fatty acid (VLCFA) ratios (C24:0/C22:0 and C26:0/C22:0), while absolute concentrations of VLCFA were normal. Genetic analysis identified biallelic variants in PEX10. Immunohistochemistry confirmed pathogenicity in the patients' cultured fibroblasts demonstrating peroxisomal mosaicism with a general catalase import deficiency as well as conspicuous peroxisome morphology as an expression of impaired peroxisomal function. We describe for the first time an elongated peroxisome morphology in a patient with PEX10-related cerebellar ataxia.A literature search yielded 14 similar patients from nine families with PEX10-related cerebellar ataxia, most of them presenting their first symptoms between 3 and 8 years of age. In 11/14 patients, the first and main symptom was cerebellar ataxia; in three patients, it was sensorineural hearing impairment. Finally, all 14 patients developed ataxia. Polyneuropathy (9/14) and cognitive impairment (9/14) were common associated findings. In 12/13 patients brain MRI showed cerebellar atrophy. Phytanic acid was elevated in 8/12 patients, while absolute concentrations of VLCFA levels were in normal limits in several patients. VLCFA ratios (C24:0/C22:0 and/or C26:0/C22:0), though, were elevated in 11/11 cases. We suggest including measurement of phytanic acid and VLCFA ratios in metabolic screening tests in unexplained autosomal recessive ataxias with cerebellar atrophy, especially when there is an early onset and symptoms are mild.

Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency-related leukodystrophy.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once. METHODS: We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈ 3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging. RESULTS: During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay. CONCLUSION: NaHB is a highly effective and safe treatment that needs further controlled studies.

Atypical presentation of sunflower epilepsy featuring an EEG pattern of continuous spike waves during slow-wave sleep.

Sunflower epilepsy is a rare photosensitive and commonly pharmacoresistant reflex epilepsy characterized by stereotyped seizures involving turning of the head towards light, similar to a sunflower turning towards the sun, and waving of the hands in front of the eyes, sometimes followed by absence seizures, myoclonic jerks, and tonic-clonic seizures. In the original description, seizures in sunflower epilepsy have been perceived as self-induced, but contemporary case series suggest that hand waving corresponds to an ictal phenomenon and not to a precipitating factor. We describe a nine-year-old girl featuring absence seizures with eye rolling or fluttering associated with hand waving movements. The chronological sequence of events based on a video-EEG-documented episode of our patient adds to the controversy surrounding the hypothesis of "self-induced" epileptic seizures in sunflower epilepsy. Shortly after epilepsy diagnosis, our patient presented with an EEG pattern of continuous spike waves in slow-wave sleep, an EEG feature that has not been described before and may relate to the cognitive deficit observed in some patients with sunflower epilepsy. Continuous spike waves in slow-wave sleep resolved, and lasting seizure freedom was achieved by a combination of ethosuximide and lamotrigine, which may be a possible alternative to valproic acid, particularly in girls and women of childbearing age. However, an attempt to taper anti-seizure drugs two years later led to seizure recurrence. We suggest performing sleep EEG recordings for sunflower epilepsy, particularly in patients with developmental stagnation or regression, to timely diagnose and treat continuous spike waves in slow-wave sleep syndrome.

Botulinum toxin type A for the treatment of equinus deformity in patients with mucopolysaccharidosis type II.

Mucopolysaccharidoses are lysosomal storage disorders that are caused by a deficiency in the enzymes that degrade glycosaminoglycans. The accumulation of glycosaminoglycans affects multiple systems, resulting in coarse facial features, short stature, organomegaly, and variable neurological changes from normal intelligence to severe mental retardation and spasticity. Effects on the musculoskeletal system include dysostosis multiplex, joint stiffness, and muscle shortening. This article reports 2 patients with mucopolysaccharidosis type II (Hunter syndrome) who showed progressive equinus deformity of the feet. Both patients were treated with intramuscular botulinum toxin type A injections in the gastrocnemius and the soleus muscles, followed by serial casting. In both patients, passive range of motion, muscle tone, and gait performance were significantly improved. Botulinum toxin type A injections followed by serial casting are a therapeutic option for contractures in patients with mucopolysaccharidosis. However, the long-term effects and the effect of application in other muscles remain unknown.

Mental relaxation improves long-term incidental visual memory.

Experimental evidence has linked increased arousal to enhanced memory retention. There is also evidence that procedures reducing arousal, i.e., mental relaxation, might improve memory, but conflicting results have been reported. To clarify this issue, we studied the effects of a single session of relaxation training on incidental visual long-term memory. Thirty-two relaxation-naive subjects viewed 280 slides without being told that there would be subsequent memory testing. Afterwards, subjects listened to a 12 min relaxation tape; 16 subjects relaxed by following the instructions (relaxation group), and the other 16 subjects pressed a button whenever a body part was mentioned (control group). While listening to the relaxation tape, high frequency heart rate variability (HRV) was greater and low frequency HRV was lower in the relaxation group, implying effective relaxation and increasing parasympathetic activation. The relaxation group had superior memory retention 4 weeks later (p = .004), indicating enhancement of long-term memory performance. This effect could not be explained by retroactive interference experienced in the control group because short-term memory performance immediately after the tape was slightly better in the control group. Retention of materials acquired after the relaxation session remained unaffected, suggesting relaxation has retrograde effects on memory consolidation. Our data demonstrate a favorable influence of relaxation on at least this aspect of learning. Our data also extend previous knowledge on the beneficial effects of ascending parasympathetic stimulation on memory retention in that enhanced long-term memory consolidation may also occur in the presence of central and descending parasympathetic activation triggered by willful psychomotor activity.