Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene.

Giant axonal neuropathy (GAN) is an autosomal recessive neurologic disorder clinically characterized by a severe polyneuropathy, CNS abnormalities, and characteristic tightly curled hair. Recently, mutations in the gigaxonin gene have been identified as the underlying genetic defect. The authors report two novel mutations confirming that GAN is caused by mutations in the gigaxonin gene and raise the question whether some mutations may cause a mild subclinical neuropathy.

Recessively inherited amyotrophic lateral sclerosis: a Germany family with the D90A CuZn-SOD mutation.

Mutations of the SOD1 gene encoding the free radical scavenging enzyme copper-zinc superoxide dismutase (CuZn-SOD) occur in patients with familial amyotrophic lateral sclerosis (ALS). Recent reports have shown homozygosity for a CuZn-SOD mutation in exon 4, the D90A (Asp90A1a) mutation. Other mutations described to date show an autosomal dominant pattern of inheritance. This is the first description of autosomal recessively inherited ALS in an out-bred population in central Europe. This study confirms the earlier described characteristic phenotype reported in D90A homozygous ALS patients in Scandinavia and supports the theory of the existence of a strong modifying factor in some cases of ALS associated with mutations in the CuZn-SOD gene.

[X-chromosomal recessive spinobulbar muscular atrophy (Kennedy type). Description of a family, clinical aspects, molecular genetics, differential diagnosis and therapy]. / Die X-chromosomal rezessive spinobulbäre Muskelatrophie (Typ Kennedy). Beschreibung einer Familie, Klinik, molekulare Genetik, Differentialdiagnose und Therapie.

The Kennedy-Syndrome is a X-linked recessive bulbospinal muscular atrophy, in some cases associated with endocrinological disturbances such as androgen resistance and diabetes mellitus. The age of onset is usually between 20 and 40. Presenting symptoms are proximal flaccid weakness, fasciculations, cramps or tremor. Disease progression is usually slow and live expectancy is normal. It is important to distinguish the Kennedy-Syndrome from amyotrophic lateral sclerosis, spinal muscular atrophy, muscular dystrophies and other types of motor neuron disease. Kennedy disease is caused by an expanded trinucleotide repeat in the androgen receptor gene. Genetic analysis allows a precise-diagnosis on an individual basis and reliable genetic counselling. An effective medical treatment does not yet exist.

Postexcitatory inhibition after transcranial magnetic stimulation of the motor cortex in patients with drug-induced parkinsonism and in healthy individuals.

The duration of the postexcitatory inhibition after transcranial magnetic stimulation was investigated in 16 patients with drug-induced parkinsonism and in 20 healthy control individuals. In the patients, the chlorpromazine-equivalent of the neuroleptic medication was determined, and the severity of the drug-induced parkinsonism was measured using the Simpson-Angus Scale score. Group comparison (U-test) revealed a significant shorter postexcitatory inhibition in patients than in control individuals. Regression analyses showed a negative correlation between the Simpson-Angus scale score and the duration of the postexcitatory inhibition. The correlation only reached significance for a group of patients who received at least one butyrophenone derivate. No clear-cut relation was found between the chlorpromazine equivalent and the postexcitatory inhibition. These results indicate that drug-induced parkinsonism shares features of genuine Parkinson's disease. Furthermore, it seems possible to assess the extrapyramidal side effect of butyrophenone derivates, but not for other neuroleptic drugs, by means of the method described.

Variation of reaction time can be reduced by the time locked application of magnetic stimulation of the motor cortex.

It was the aim of this study to determine the influence of non-invasive magnetic stimulation on the performance of a visually induced reaction task. The experiment was performed in 8 healthy volunteers. After a visual stimulus subjects had to move their thumbs as soon as possible. The muscular reaction was recorded with surface EMG on both sides. After the visual go-signal a magnetic stimulus (Fig. 8 coil) was applied above the right or left motor cortex at varying time intervals (30 and 110 ms). The magnetic stimulus was randomly given or not. Short time intervals between visual and magnetic stimulus induced a shortening, long intervals induced a prolongation of the reaction time. The contralateral reaction time was always longer than the ipsilateral one. Compared with the reaction times without magnetic stimulation, the intraindividual standard deviation of the reaction times was markedly reduced by the application of the magnetic stimulation. This reduction was greater in ipsilateral than in contralateral recordings. The kind of the instruction had additional modifying effects.

Somatosensory evoked potentials after magnetic stimulation at different points of the body in normal subjects and in patients with syringomyelia.

Somatosensory evoked potentials (SEPs) were elicited by magnetic stimulation of the tibial nerve, gastrocnemic muscle and by stimulation over the spinous processes of lumbar vertebra 5 (L 5), thoracic vertebra 9 (Th 9) and cervical vertebra 7 (C 7). The first SEP-positivity (P1-latency) was measured in a group of 20 controls and in another group of 18 patients with syringomyelia. The P1-latencies of the latter group following the stimulations over Th 9 and C 7 were significantly longer than those of the controls. Furthermore a correlation between electrophysiological findings and clinical data of the patients could be proven. Thus the method emerged as an appropriate tool for the investigation of the central part of the sensory system and for the diagnosis of spinal abnormalities.

Effect of L-dopa on visual evoked potentials and neuropsychological tests in adult phenylketonuria patients.

Eight adult, untreated patients with classical phenylketonuria received L-dopa and a decarboxylase inhibitor for 2 weeks. No effect of L-dopa therapy on choice reaction time tasks, sustained attention, frontal lobal function as well as latencies of visual evoked potentials was found. The results raise the question if adult patients with phenylketonuria really suffer from functional dopamine deficiency.

Involvement of the autonomic nervous system in patients with syringomyelia--a study with the sympathetic skin response.

In order to determine the function of the autonomic nervous system in syringomyelia, the sympathetic skin response (SSR) was performed in 13 patients with syringomyelia and 20 healthy controls. SSR was recorded from both palms and soles. In patients with syringomyelia, we found absent responses, prolonged latencies and reduced amplitudes. SSRs could be recorded in 15 out of the examined 26 upper extremities. The latencies were prolonged in 12 of these cases. In the lower limbs, 11 SSRs could be obtained. In 4 of these cases the latencies were prolonged. The SSR latencies recorded from the palms and soles were both significantly prolonged (p < 0.05) and the amplitudes were reduced (p < 0.05) as compared to normal persons. Our data strongly suggest involvement of the autonomic nervous system in syringomyelia as assessed by the SSR response (in upper and lower extremities). In our patients, the extent of autonomic dysfunction was not related to the stage or the duration of disease.

Sympathetic skin response in patients with amyotrophic lateral sclerosis.

To determine a possible involvement of the autonomic nervous system in amyotrophic lateral sclerosis (ALS), measurement of the sympathetic skin response (SSR) was performed in 15 patients with definite ALS. Findings were compared with those in 20 normal controls. In ALS patients the mean SSR latencies recorded from the palms and soles were both significantly prolonged (p < 0.05) and the amplitudes were reduced as compared with normal persons. In 5 patients, SSR potentials were completely lacking in one or even more extremities. Our data strongly suggest subclinical involvement of the autonomic nervous system in ALS as assessed by the SSR response. In our patients the extent of autonomic dysfunction was not related to the stage or the duration of disease.

[The idiopathic QT syndrome as the cause of epileptic and nonepileptic seizures]. / Das idiopathische QT-Syndrom als Ursache epileptischer und nicht epileptischer Anfälle.

The long QT syndrome (LQTS) is characterized by a pathological lengthening of the corrected QT interval on the surface ECG and the occurrence of syncopal attacks, sometimes presenting as a seizure disorder. They are caused by ventricular tachycardia of the torsade de pointes type, an arrhythmia that is also responsible for the high incidence of sudden death among these patients. Besides the acquired forms of LQTS which are transient (e.g. therapy with QT-prolonging drugs), congenital variants (Romano-Ward syndrome, Jervell/Lange-Nielsen syndrome, sporadic form) can occur as well. The latter mostly become manifest during childhood or adolescence. Because the syndrome is rare, it is often not included in the primary differential diagnosis of syncope. Thus, misinterpretation as epilepsy may occur. Especially if siblings are affected, a genetic epilepsy may be diagnosed. However, the correct diagnosis can be made by standard ECG methods. Early recognition of the syndrome is very importance because of prognostic and therapeutic consequences. In this article, two cases of idiopathic LQTS are presented. Problems regarding differential diagnosis and therapy are discussed.

Inhibitory period and late muscular responses after transcranial magnetic stimulation in healthy children.

Transcranial magnetic stimulation (TMS) was investigated in 24 healthy children between the ages of 3 and 14 years in order to study late muscular responses (as they are observed in adults) as a function of age and maturation. Muscular responses were recorded bilaterally from the biceps muscle. An early muscular response and several late phenomena can be elicited in children. (i) An inhibitory period following the primary response could preferentially be recorded contralaterally. (ii) During facilitation, a late response was recorded bilaterally. (iii) Without facilitation (during 'relaxation'), late responses were recorded bilaterally with a latency of between 50-400 ms. The latency of the latter responses depended on the age of the children, and may therefore be useful in monitoring the maturation of the central motor system in infants. Due to small side-to-side differences, the inhibitory period may be of diagnostic value in children for detection of unilateral dysfunction of the central nervous system.

Cerebellar herniation in syringomyelia: relation between tonsillar herniation and the dimensions of the syrinx and the remaining spinal cord. A quantitative MRI study.

The dimensions of the syrinx, the remaining spinal cord and the degree of cerebellar herniation were analyzed by one- and two-dimensional MRI studies in 22 patients with syringomyelia. A deep and/or broad cyst tends to be a long one. The dimensions of the syrinx and the spinal cord have an inverse relationship. The degree of cerebellar herniation is not related to the longitudinal or transverse extension of the cyst or the ratio cyst/cord or the remaining spinal cord (neither for diameters nor for cross-sectional areas). The dimensions of cysts are not significantly greater in patients with tonsillar herniation than in patients without. We conclude that cerebellar herniation is not a major prognostic factor and should not be overestimated for the development and progression of the disease.

[Comparison of D2 receptor scintigraphy (123I-IBZM) with cerebral perfusion (99m-Tc-HMPAO) in extrapyramidal disorders]. / D2-Rezeptorszintigraphie (123J-IBZM) im Vergleich zur zerebralen Perfusion (99mTc-HMPAO) bei extrapyramidalen Erkrankungen.

The aim of this SPECT study was to determine whether there is a correlation between rCBF (99mTc-HMPAO) and D2 receptor binding (123I-IBZM) in disorders of the extrapyramidal system and in which situation the 99mTc-HMPAO scan could predict the outcome of the 123I-IBZM study. 13 patients with Parkinson's syndrome and 13 patients with hyperkinetic extrapyramidal disorders were studied. In all patients the two SPECT studies were performed within 2-7 days. ROIs were placed over the basal ganglia (BG), the frontal cortex (FC) and the cerebellum (CE). The ratios BG/FC and BG/CE were calculated. In both groups the scatter was lower when the frontal cortex was used as reference region. Among the patients with hyperkinetic extrapyramidal disorders the two patients with Huntington's chorea had lower rCBF and D2 receptor binding compared to other hyperkinetic extrapyramidal disorders. There was no correlation between D2 receptor binding and rCBF in the basal ganglia. The 99mTc-HMPAO studies did not provide clinically useful information, except in Huntington's chorea.

White matter abnormalities in patients with treated hyperphenylalaninaemia: magnetic resonance relaxometry and proton spectroscopy findings.

In order to further clarify the pathogenesis and clinical significance of MRI white matter abnormalities in treated hyperphenylalaninaemia (HPA), ten patients (seven type I HPA, two type II and one type III) underwent T2 relaxometry (n = 8) and/or 1H spectroscopy (n = 7) in addition to conventional MR spin-echo imaging at 1.5 T. Two patients with severe MRI abnormalities had repeat examinations during and after a 6- to 8-month period of strict diet control. The clinical evaluation included a detailed neurological examination. In nine out of ten patients visual evoked potentials (VEP) were obtained parallel to the MR examination. MR imaging demonstrated typical symmetrical areas of prolonged T2 relaxation time predominantly in the posterior periventricular white matter in all but one of type I and II patients. There was no consistent relationship between MRI findings and time of diagnosis/initiation of therapy, IQ or visual evoked potential changes. MRI abnormalities tended to be more severe in patients with poor dietary control and high current plasma phenylalanine levels, whereas a normal MRI was found only in patients with plasma phenylalanine levels continuously below 0.36 mmol/l. There was marked regression of MRI abnormalities already after 3 months of strict diet control. T2 relaxometry showed a bi-exponential behaviour of T2 in the affected white matter, with a slow component of about 200-450 ms, indicating an increase in free (extracellular) water. 1H spectroscopy revealed no signs of severe neuronal damage. We conclude, that the observed white matter changes in treated HPA probably represent reversible structural myelin changes rather than permanent demyelination.