Petra Baum

A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy.

To compare the effectiveness of controlled‐released carbamazepine (CR‐CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy.

Dysfunction of Autonomic Nervous System in Childhood Obesity: A Cross-Sectional Study

Objective To assess the distribution of autonomic nervous system (ANS) dysfunction in overweight and obese children. Methods Parasympathetic and sympathetic ANS function was assessed in children and adolescents with no evidence of impaired glucose metabolism by analysis of heart rate variability (low frequency power ln(LF), high frequency power, ln(HF); ln(LF/HF) ratio, ratio of longest RR interval during expiration to shortest interval during inspiration (E/I ratio), root mean square of successive differences (RMSSD); sympathetic skin response (SSR); and quantitative pupillography (pupil diameter in darkness, light reflex amplitude, latency, constriction velocity, re-dilation velocity). The relationship of each ANS variable to the standard deviation score of body mass index (BMI-SDS) was assessed in a linear model considering age, gender and pubertal stage as co-variates and employing an F-statistic to compare the fit of nested models. Group comparisons between normal weight and obese children as well as an analysis of dependence on insulin resistance (as indexed by the Homeostasis Model Assessment of Insulin Resistance, HOMA-IR) were performed for parameters shown to correlate with BMI-SDS. Statistical significance was set at 5%. Results Measurements were performed in 149 individuals (mean age 12.0 y; 90 obese 45 boys; 59 normal weight, 34 boys). E/I ratio (p = 0.003), ln(HF) (p = 0.03), pupil diameter in darkness (p = 0.01) were negatively correlated with BMI-SDS, whereas ln(LF/HF) was positively correlated (p = 0.05). Early re-dilation velocity was in trend negatively correlated to BMI-SDS (p = 0.08). None of the parameters that depended significantly on BMI-SDS was found to be significantly correlated with HOMA-IR. Conclusion These findings demonstrate extended ANS dysfunction in obese children and adolescents, affecting several organ systems. Both parasympathetic activity and sympathetic activity are reduced. The conspicuous pattern of ANS dysfunction raises the possibility that obesity may give rise to dysfunction of the peripheral autonomic nerves resembling that observed in normal-weight diabetic children and adolescents.

Phenotype of matrin-3-related distal myopathy in 16 German patients.

To characterize the phenotype of patients with distal myopathy with vocal cord and pharyngeal weakness due to the p.S85C mutation in the matrin‐3 gene (MATR3, Mendelian Inheritance in Man 164015). Recently, it has been suggested that patients with this mutation may suffer from familial amyotrophic lateral sclerosis.

Unusual triplet expansion associated with neurogenic changes in a family with oculopharyngeal muscular dystrophy.

The occasional observation of neurogenic features in oculopharyngeal muscular dystrophy (OPMD) is unclear both in nosological and in etiological respects. Studies are reported here of a family with autosomal‐dominant OPMD involving seven members over three generations. In three of them muscle biopsies were performed. Two of the patients (a 45‐year‐old sister and a 57‐year‐old brother of the third generation) were studied in more detail and, in addition to the typical changes of OPMD, showed a neurogenic component both by electrophysiology and morphology. Molecular genetic investigations revealed a repeat unit of (GCG/GCA)13 in the first exon of the poly(A)binding‐protein2 gene in both siblings. A possible association of this unusually long triplet repeat extension with the atypical phenotype is considered and has to be verified in other cases.

Diabetic neuropathy in patients with “Latent Autoimmune Diabetes of the Adults” (LADA) compared with patients with type 1 and type 2 diabetes

Abstract.Objective: In previous studies, a lower incidence of diabetes-related complications such as diabetic neuropathy has been reported in patients with early stages of type 1 diabetes compared with type 2 diabetes. The aim of this study was to compare the prevalence of diabetic neuropathy in patients with manifestation of a slow onset type 1 diabetes in adulthood – latent autoimmune diabetes in adults (LADA) – with classical type 1 and type 2 diabetes patients. Research Design and Methods: Altogether, 37 patients (14 LADA, 9 type 1 and 14 type 2 diabetes) with short term diabetes (duration < 5 years) were investigated for diabetic neuropathy on the basis of clinical and neuroelectrophysiological evaluations. The neurological functions were evaluated by a standardized questionnaire and clinical examination. In electrophysiological evaluations the different nerve fibres were investigated using motor and sensory nerve conduction studies, quantitative thermotesting, vibratometry and autonomic function tests (heart rate variability). Results: LADA patients had a significantly lower clinical examination score (p = 0.008), cardiorespiratory reflex index (p = 0.009) and cold perception threshold index (p = 0.004). The neurological symptom score, the indices of motor and sensory nerve conduction, the index of thermotesting (warm perception threshold) and the vibratometry showed a trend to higher values in LADA patients than in type 2 diabetes patients. There were no significant differences between LADA and type 1 diabetes patients. Conclusions: LADA patients had fewer features of diabetic neuropathy than type 2 diabetes patients in the early stages of disease, thus being more similar to classical type 1 diabetes patients who normally develop diabetic neuropathy rather late.

Recurrent reversible cerebral edema after long term immunosuppression with tacrolimus

Sirs: Tacrolimus (FK506) is a potent immunosuppressive agent frequently used for the prevention of organ transplant rejection. The neurological manifestations of tacrolimus toxicity are usually mild, but occasionally can be severe, including aphasia, confusion, seizures and coma. These side effects have mainly been described in the early post-transplant period [1, 2, 3]. We present an unusual case of recurrent severe generalized cerebral edema which occurred 46 months after initiation of tacrolimus medication following renal transplantation. A 52-year old woman was admitted 46 month after renal transplant because of two generalized tonic-clonic seizures and decreased consciousness that were preceded by two days of headaches and nausea. Her past medical history consisted of diabetes mellitus type II, mild hypertension, and hypothyroidism. On admission she was somnolent but became increasingly more alert and was communicable after 12 hours. The Tacrolimus level was measured at 6.7 ng/ml (normal range: 5–20 ng/ml). Beside callosal lipoma, a computed tomography (CT) showed moderate posterior reversible encephalopathy syndrome (PRES). MRI and MR angiography excluded sinus thrombosis and vasculitis. Laboraty evaluation did not reveal significant abnormalities. Over the next two days her course deteriorated rapidly and she became comatose with fixed pupils, loss of the left corneal reflex, and absence of the oculocephalic reflex. Cerebrospinal fluid (CSF) analysis was normal except for increased protein (630 mg/l). Protein analyses was most compatible with a disruption of the blood-brain-barrier. Tacrolimus level in the CSF was not measured. CT demonstrated generalized cerebral edema – predominantly in the occipital white matter including the occipital cortex – with obliteration of the basal cisterns. On the same day, somatosensory evoked potentials of the median nerve (SSEP) showed a complete loss of the cortical response (N20) on both sides (Fig. 1). Because of her condition all medications including tacrolimus were discontinued. Six days later (day 11) the patient was awake and communicable. CT showed resolution of the generalized cerebral edema but a moderate degree of PRES remained. An almost normal cortical response (N20) was measured by SSEP. At this point, her previous medications including tacrolimus were restarted. During the next two weeks her neurological status worsened again. By day 25 she was comatose and CT again revealed generalized cerebral edema. The SSEPs were delayed and showed a barely detectable amplitude. Tacrolimus (level 5,7 ng/ml) was then withdrawn and subsequently her neurological status improved. By day 31 CT showed resolution of the cerebral swelling but these were remaining white matter lesions (Fig. 2). We discharged the patient to a rehabilitation facility. Four months later she was communicative with tetraplegia and upper and lower cranial nerve deficits. Tacrolimus is increasingly used as an immunosuppressive agent [4]. It is chemically unrelated to cyclosporine A (CsA) but has similar properties and adverse effects including neurotoxicity. It therefore may present as the clinico-neuroradiological entity called PRES [5]. We present an extreme example of neurotoxicity but with resolution of dramatic neuroradiologic feaLETTER TO THE EDITORS

Hot-spot KIF5A mutations cause familial ALS

Brenner et al. show that mutations in a C-terminal hotspot of kinesin-5A (KIF5A) can cause a classical ALS phenotype. Experiments using patient-derived cell lines suggest haploinsufficiency as the molecular genetic mechanism. This underlines the relevance of intracellular transport processes for ALS, and is important for clinico-genetic diagnosis and counselling.

Effect of a 1-Year Obesity Intervention (KLAKS Program) on Preexisting Autonomic Nervous Dysfunction in Childhood Obesity:

Childhood obesity may involve autonomic nervous system dysfunction. Whether it improves following weight loss remains unclear. Thirty-one obese children (body mass index standard deviation scores 2.33 ± 0.47; age 11.2 ± 2.0) completed a 1-year lifestyle intervention (KLAKS: Concept Leipzig: Adiposity Therapy for School-Aged Children). Anthropometric/biochemical parameters and autonomic nervous system function (heart rate variability, quantitative pupillography) were assessed at baseline and follow-up. A multivariate model for changes in body mass index standard deviation scores considered age, gender, and changes in autonomic nervous system function. Weight status (Δ body mass index standard deviation scores: 0.16 [0.05, 0.29], P = .008), glycemic control, and free fatty acids (all P < .05) improved after the intervention. Redilation velocity increased by 0.22 mm/s [0.06, 0.38] (P = .008), and changes tended to be negatively associated with Δ body mass index standard deviation scores (P = .08 [–0.61, 0.03]). Relative reflex amplitude (23.4 vs 26.3, P = .004) and constriction velocity (4.97 mm/s vs 5.47 mm/s, P < .001) also improved. Our data provide preliminary evidence that lifestyle-intervention induced improvement of weight status/metabolic risk factors may ameliorate some parameters of autonomic nervous system dysfunction in childhood obesity.

Late onset dHMN II caused by c.404C>G mutation in HSPB1 gene.

Distal hereditary motor neuropathy (dHMN) type II is genetically heterogeneous. We report three siblings of a German family with late onset distal motor neuropathy due to the c.404C>G mutation in heat‐shock 27‐kDa protein 1 gene (HSPB1/HSP27). A 36‐year‐old mutation carrier, daughter of one sibling, did not present any clinical or electrophysiological abnormalities. The index patient (oldest brother) developed weakness of the distal lower limbs and nocturnal muscle cramps at the age of 54. After 5 years this patient developed an l‐DOPA‐responsive hypokinetic rigid syndrome, establishing a diagnosis of Parkinsons disease. Although none of the three other mutation carriers displayed Parkinsonian signs, a pathogenic relationship with Parkinsons disease remains a possibility, based on the known molecular pathology of HSPB1. The rare pathogenic HSPB1 c.404C>G mutation may predispose for late‐onset of dHMN type II.

Critical-illness-Myopathie und -Neuropathie (CRIMYN)

BACKGROUND Critical Illness Myopathy and Neuropathy (CRIMYN) frequently coexist with severe sepsis and is associated with prolonged weaning from mechanical ventilation and prolonged ICU length of stay. We aimed to classify different levels as well as patterns of impairment with regard to electrophysiological disturbances in CRIMYN patients by cluster analysis. METHODS A total of 30 patients with sepsis/SIRS were studied prospectively. Motor and sensory conduction studies were performed from six motor and four sensory nerves on a weekly basis from admission until discharge and finally after 6 months. A control group of 63 healthy persons was examined simultaneously using the same criteria. Different patterns of electrophysiological disturbances were classified by cluster analysis based on differences to reference values of 20 parameters, compound muscle action potential (CMAP), sensory nerve action potential (SNAP) and motor and sensor conduction velocity (NCV). RESULTS Four different clusters were identified: cluster 1 showing normal values for CMAP, SNAP and NCV in all nerves (3 patients and all test persons), cluster 2 showing pathological values for CMAP in the lower extremities and the other parameters were normal (5 patients), cluster 3 showing moderately pathological values for CMAP, SNAP and sensory NCV in upper and lower extremities and motor NCV in lower extremities (12 patients) and cluster 4 showing severe disturbances of CMAP, SNAP and NCV in upper and lower extremities (10 patients). CONCLUSION A total of four different clusters of electrophysiological impairment can be identified in patients with sepsis/SIRS, which enables further differentiation of the severity of neuromuscular disturbances in sepsis-associated organ failure. This might be useful as a prognostic parameter and can be correlated with additional clinical and paraclinical parameters related to sepsis.