Characterization of basal ganglia dysfunction in Leber 'plus' disease.
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Adult↗
Biomedical subjects
R Benecke
Publications and source records attributed to R Benecke.
Idiopathic torsion dystonia: assignment of a gene to chromosome 18p in a German family with adult onset, autosomal dominant inheritance and purely focal distribution.
Idiopathic torsion dystonia (ITD) is a group of movement disorders which is usually inherited in an autosomal dominant manner with reduced penetrance. Most patients with ITD present with focal dystonia at adult age. However, thus far, this common subform remained unmapped chromosomally. In contrast, a rare early onset, more generalized form of ITD has been mapped to chromosome 9q34. Our linkage study in a large pedigree with seven definitely affected, six possibly affected and 16 phenotypically unaffected family members assigns an ITD gene for the common focal form with a maximal lod score of 3.17 to the region telomeric of D18S1153 on chromosome 18p.
Adult↗
Adult-onset complex partial seizures as the presenting sign in colpocephaly: MRI and PET correlates.
In a 30-year-old man, adult-onset complex partial seizures were associated with colpocephaly as evident from magnetic resonance images. The structurally normal lateral neocortex of the right temporal lobe showed a severe reduction in regional glucose consumption corresponding to the epileptic focus as judged from the surface electroencephalogram. In contrast to previously reported patients, this patient had no focal neurological signs, and neuropsychological testing revealed normal general intelligence. Thus, this patient adds a benign variant to the clinical spectrum of this cerebral developmental disorder.
Adult↗
Magnetic stimulation in the assessment of peripheral nerve disorders.
Relatively pain-free excitation of both superficial and deep nerves in the assessment of nerve conduction velocity is the main advantage of magnetic stimulation over conventional electrical stimulation. General utility of this technique has often been called into question by a number of authors because of difficulties in obtaining supramaximal responses or in determining the exact site of impulse generation when stimulating a peripheral nerve distally. Meanwhile, magnetic stimulation of the cervical and lumbar roots has become a routine procedure for the assessment of peripheral conduction time and is combined with transcranial magnetic stimulation of the motor cortex in the assessment of central conduction time. Recent developments in magnetic coil and stimulator design have improved the focality of the stimulus, so that selective supramaximal stimuli can be delivered to commonly studied peripheral nerves in the upper and lower limbs, both at proximal and distal segments. Furthermore, the introduction of small figure-8-shaped coils enables safe diagnosis of chronic compression syndromes with exact assessment of conduction velocities over short distances of peripheral nerves. The ease of application of magnetic stimulation and the absence of pain for the patient make magnetic stimulation a particularly attractive method for also investigating patients with demyelinating polyneuropathies, and will certainly replace conventional electrical stimulation in the near future.
Demyelinating Diseases↗
Proximal myotonic myopathy syndrome in the absence of trinucleotide repeat expansions.
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DNA Mutational Analysis↗
Stiff-person syndrome with anti-glutamic acid decarboxylase autoantibodies: complete remission of symptoms after intrathecal baclofen administration.
A female patient, aged 61 years, who developed a severe immobilizing stiff-person syndrome in conjunction with insulin-dependent diabetes mellitus, is described. In addition to the typical clinical symptoms, diagnosis was proven by the presence of autoantibodies against glutamic acid decarboxylase in serum and cerebrospinal fluid. Symptomatic treatment with continuous intrathecal application of baclofen administered by a subcutaneous pump resulted in rapid clinical improvement so that the patient became ambulatory. Intermittent withdrawal from intrathecal baclofen therapy led to complete remanifestation of stiff-person syndrome within 18 h; after re-introduction of intrathecal therapy stiffness disappeared completely within 48 h. The clinical course has been stable now for over 24 months and stiffness has completely disappeared. The effect of baclofen in this patient is discussed in the light of the suggested pathophysiological mechanisms in stiff-person syndromes.
Autoantibodies↗
Epileptic seizures triggered directly by focal transcranial magnetic stimulation.
Focal, secondarily generalizing, epileptic seizures were released by magnetic stimulation in a patient with focal epilepsy. The stimulation induced seizures had a similar clinical appearance to the patient's spontaneous seizures. They were released exclusively by an angulated "figure-of-8" coil which stimulates the brain more focally as compared to the commonly used flat round coil. The epileptic focus could be located in the left frontal cortex by electroencephalographic recordings, by magnetic resonance and by positron emission tomography imaging. Functional assessment of the motor system by transcranial magnetic stimulation (TMS) disclosed markedly prolonged electrical silence of contralesional electromyographic activity following the early excitation. This is the first EMG-documented demonstration of a focal motor seizure directly triggered by magnetic brain stimulation.
Adolescent↗
Inhibitory phenomena in individual motor units induced by transcranial magnetic stimulation.
It is well known that a silent period (SP) can be observed in voluntary tonic EMG activity starting directly after the initial early response when magnetic stimuli are delivered through the skull over the contralateral primary motor cortex. It is, however, unknown as to how an individual motoneurone (MN) contributes to the SP observed in the surface EMG. The present investigation was conducted to investigate inhibitory phenomena at the level of individual motor units. It demonstrates that the duration of the SP in single motor units is inhomogeneously distributed within the pool of active MNs. At various stimulation strengths, SP durations in single motor units can be similar or longer when compared to that observable in surface EMG records. In some motor units, which show low thresholds for early excitation and appearance of the SP, durations of SP can exceed 1000 msec. The length of suppression of spontaneous MN firing is maximal at stimulus intensities a little higher than those required for an early excitatory response. Although in general thresholds for early excitation and appearance of SPs are similar, at threshold stimulation in a number of trials inhibitory effects on the firing of voluntarily activated motoneurones were present, even in the absence of early excitations. This proves the independent nature of inhibitory as opposed to excitatory effects induced by transcranial magnetic stimulation. An SP in the absence of early excitation underlines its cortical origin. Inhibition and excitation of single MNs were maximal over the same small scalp area. We suggest that cortical inhibitory control plays an important role in the organization of natural movements.
Adult↗
The silent period induced by transcranial magnetic stimulation in muscles supplied by cranial nerves: normal data and changes in patients.
The silent period induced by transcranial magnetic stimulation of the sensorimotor cortex (Magstim 200, figure of eight coil, loop diameter 7 cm) in active muscles supplied by cranial nerves (mentalis, sternocleidomastoid, and genioglossus) was studied in 14 control subjects and nine patients with localised lesions of the sensorimotor cortex. In the patients, measurements of the silent period were also made in the first dorsal interosseus and tibialis anterior muscles. In the controls, there was a silent period in contralateral as well as ipsilateral cranial muscle and the duration of the silent period increased with increasing stimulus intensities. The mean duration of the silent period was around 140 ms in contralateral mentalis muscle and around 90 ms in contralateral sternocleidomastoid muscle at 1.2 x threshold stimulation strengths. Whereas the duration of the silent period in ipsilateral mentalis muscle was shorter than on the contralateral side it was similar on both sides in sternocleidomastoid muscle. In patients with focal lesions of the face associated primary motor cortex and corresponding central facial paresis, the silent period in mentalis muscle was shortened whereas it was unchanged or prolonged in limb muscles (first dorsal interosseus, tibialis anterior) with stimulation over the affected hemisphere. By contrast, in a patient with a lesion within the parietal cortex, the silent period in mentalis muscle was prolonged with stimulation of the affected side.
Adult↗
The silent period after transcranial magnetic stimulation is of exclusive cortical origin: evidence from isolated cortical ischemic lesions in man.
In two representative patients suffering from focal isolated ischemic lesions of the arm-associated (patient 1) or leg-associated (patient 2) primary motor cortex excitatory responses (motor evoked potentials, MEPs) and inhibitory phenomena (silent period, SP) following transcranial magnetic motor cortex stimulation (TMS) are demonstrated. Furthermore, supramaximal peripheral nerve stimulations for testing spinal inhibitory actions were performed. Results were compared to a control group of 12 normal subjects. In patient 1, SP induced by TMS in the clinically affected left extensor carpi radialis muscle (ECR) was lacking in the presence of an only marginally reduced MEP and a normal spinal silent period in this muscle. Normal MEPs and SP durations were observed in the right ECR and in the first dorsal interosseus (FDI) and anterior tibial (TA) muscles on both sides. Similarly, in patient 2 a loss of SP induced by TMS in the clinically affected right TA was observed with normal SP durations in the left TA and both FDI muscles and normal MEP amplitudes in all muscles studied. It is concluded that both early and late phases of SP induced by TMS are of cortical origin and generated in the primary motor cortex.
Aged↗
Inhibitory actions of motor cortex following unilateral brain lesions as studied by magnetic brain stimulation.
Noninvasive transcranial magnetic stimulation (TMS) of the motor cortex not only induces short-latency, motor-evoked potentials (MEP) in contralateral muscles, but also inhibitory phenomena. One type of inhibitory action appears directly after the MEP in contralateral muscles and can be visualized by blockade of tonic, voluntary electromyographic (EMG) activity (postexcitatory inhibition, PI). Evidence for a cortical origin of PI, especially in its later part, was derived from double cortical stimulation in previous studies and is further supported by examination of PI in patients with focal hemispheric unilateral brain lesions in the present study. Thirty patients with different sites of vascular or tumour lesions were studied by TMS. In 6 patients with circumscribed lesions of the primary sensorimotor cortex a significant shortening of PI to contralateral muscles was observed. In 7 patients with focal lesions of the thalamus or internal capsule, in 6 patients with lesions of the premotor cortex and in 5 patients with lesions restricted to the parietal or temporal lobe, a significant prolongation of PI to the contralateral muscles was detected. Six patients with transient ischemic attacks showed either prolongation or shortening of PI. We conclude that PI is predominantly generated in the primary motor cortex, correspondingly its damage causes shortening of PI. In contrast, damage to brain areas that project to the primary motor cortex is followed by prolongation of PI. This remote effect on the primary motor cortex may result from disinhibition of cortical interneurones.
Adult↗
Cerebral network underlying unilateral motor neglect: evidence from positron emission tomography.
In 4 male patients (age range 50-73 years) with unilateral motor hemineglect as a sequelae of circumscribed cerebral infarction, depressions of the regional cerebral glucose metabolism (rCMRGlu) were mapped to identify the metabolically affected cerebral structures. Motor neglect was defined according to Castaigne by lack of spontaneous and pain-induced motor activity on one side of the body in the absence of paresis, pyramidal signs, and sensory loss. The depressions of the rCMRGlu as determined by positron emission tomography (PET) were found to exceed the areas of structural damage but to be restricted to the affected cerebral hemisphere. Significant mean rCMRGlu depressions followed a focal pattern involving the premotor, prefrontal, parietal and cingulate cortex, as well as the thalamus. In correspondence to the lack of significant mean rCMRGlu depressions in primary sensorimotor cortex, basal ganglia, and cerebellum the cortico-spinal pathway was spared as indicated by preserved magnetic evoked motor potentials. Our data provide evidence suggesting that motor hemineglect is a disturbance in a cerebral network of higher order cortical areas subserving motor activity in the presence of an intact motor cortical output system.
Aged↗
Motor impairment in Wilson's disease. 3: The clinical impact of pyramidal tract involvement.
Magnetic brain stimulation was performed on 24 patients with Wilson's disease (WD). Responses to the right and left first dorsal interosseus muscle (FDI) and to the right and left tibialis anterior muscle (TA) were analysed. In 45% of the patients prolonged central motor conduction times (CCTs) to the FDIs were found, whereas only 12% of the patients presented with prolonged CCTs to the TA muscles. No consistent significant correlations between copper metabolism and pyramidal tract function tested by magnetic brain stimulation were found. An improvement of CCTs and response amplitudes with copper elimination therapy was observed only at early phases of therapy. There was no correlation with duration of therapy or neurological symptoms. Thus magnetic brain stimulation turns out to be sensitive to detect subclinical pyramidal tract impairment in WD but seems to test a too specific aspect of motor impairment in WD to reflect the overall neurological status of the patients. Therefore, it has to be combined with other tests to be used for therapy control.
Adolescent↗
On the origin of the postexcitatory inhibition seen after transcranial magnetic brain stimulation in awake human subjects.
Non-invasive transcranial magnetic stimulation (TMS) of motor cortex induces motor evoked potentials in contralateral muscles which are thought to be conducted by the corticospinal tract. Furthermore, inhibitory actions can be elicited by TMS which appear directly after the motor evoked potential (postexcitatory inhibition, PI) and can be visualized by blockade of tonic voluntary EMG activity. It was the aim of the present study to answer the questions of whether this inhibitory action is mainly of cortical or of spinal origin, which brain area generates this inhibition, and whether the duration of PI differs between proximal and distal muscles. Experiments were performed on a total of 34 healthy volunteers. Brain stimuli were delivered with a Novametrix Magstim 200HP with a maximum output of 2.0 T, and stimulation was performed during tonic voluntary activation of the muscle under study. Stimulation strength was 1.5 times threshold level. Duration of PI was defined as the time from the onset of the motor evoked potential to the reoccurrence of the EMG background activity. PI was found more pronounced in distal hand muscles than in proximal arm and leg muscles. The largest PI values were observed when the primary motor cortex was stimulated. To test the excitability of the spinal motoneurones during PI, cortical double stimulation at various intervals was performed and the soleus H-reflex was evoked at different intervals after cortical stimulation. Neither test revealed a decrease in the excitability of the spinal motoneurones during PI. These findings imply that spinal segmental inhibitory action cannot account for PI and that, most probably, inhibitory actions within the motor cortex play a major role in the genesis of PI.
Arm↗
Electron transfer complexes I and IV of platelets are abnormal in Parkinson's disease but normal in Parkinson-plus syndromes.
Using a technique which requires only 100 ml blood we investigated the electron transfer complexes (ETC) I, III and IV in platelet mitochondria of 44 control subjects, 27 patients with idiopathic Parkinson's disease and eight patients with Parkinson-plus syndromes due to multiple system atrophy. In both control subjects and patients, ETC measurements were repeated at intervals of several months. The activities varied considerably among normal subjects, but intra-individual variation of ETC activities were low at repetitive measurements. In normal subjects there was no correlation between enzyme activities and age or training state. There was no difference in enzyme activities between smokers and non-smokers in the control group. Complex I activity was lower in Parkinson's disease patients than in controls (14 versus 29 nmol/min/mg platelet protein; P < 0.001). Furthermore, the group difference in complex IV activity also reached statistical significance (83 versus 58 nmol/min/mg platelet protein; P < 0.001). Additionally, in some Parkinson's disease patients, activities of complex III were low and lay outside the control range, but the group difference did not reach significance. There was no correlation between complex I activity and disease duration or severity as well as the daily L-dopa dose in Parkinson's disease patients. Repeated measurements in five Parkinson's disease patients in the earliest stages of their illness demonstrated that the decrease in complex I and IV activities can develop rapidly within 1 year. In Parkinson-plus patients suffering from multiple system atrophy the ETC activities were normal.
Aged↗
Persistent chorea after recurrent hypoglycemia. A case report.
In a 72-year-old woman with a 33-year history of diabetes mellitus bilateral chorea had occurred after a series of hypoglycemic comas at the age of 58. The choreiform movements remained untreated, persisted more than 10 years and inspite of intermittent exaggeration were tolerated by the patient. Except for the hyperkinetic movements, neurological examination of this patient was otherwise normal as was cranial computer tomography.
Aged↗
Electron transfer complex I defect in idiopathic dystonia.
It has been suggested that dystonia is caused by an autosomal gene with reduced penetrance and a consequent biochemical abnormality affecting cell activity within the basal ganglia. No consistent biochemical disturbance has been identified. In the present study, activities of the mitochondrial electron transfer complexes were measured in platelets of 31 patients with idiopathic dystonia. Enzyme assays of these patients were compared to measurements in 28 control subjects. A significant decrease of complex I activity was observed in the majority of the patients, whereas the activities of other electron transfer complexes were normal. The severity of the complex I defect was more pronounced in patients with the segmental or generalized form than in those with focal dystonia. Complex I activity was not age dependent in the patients or control subjects. Although the electron pathway in complex I is disturbed in patients with idiopathic dystonia, complex I protein content seems to be normal. Whether abnormalities of complex I activity play a role in the pathogenesis of idiopathic dystonia remains to be determined.
Adult↗
Motor responses evoked by magnetic brain stimulation in psychogenic limb weakness: diagnostic value and limitations.
The latencies and amplitudes of responses evoked by magnetic brain stimulation (magnetic evoked potentials, MEP) in the first dorsal interosseus and the anterior tibial (TA) muscles were investigated in 15 patients with psychogenic limb weakness and in 50 patients with limb weakness due to established organic central nervous system disease. Of the patients with psychogenic limb weakness, 3 presented with upper limb monopareses, 2 with lower limb monoparesis, 4 with hemipareses, 4 with parapareses and 2 with paraparesis. All patients with psychogenic weakness had MEP in arm and leg muscles with latencies within the normal range. MEP amplitudes were also normal except for 1 patient in whom the response amplitude in the TA of the plegic limb was reduced. In patients with limb weakness due to established organic disease, MEP were frequently but not invariably abnormal. In patients with plegic (i.e. completely paretic, MRC grade 0) muscles due to organic disease, MEP always were clearly abnormal. Normal MEP were sometimes elicited from paretic muscles, more commonly in association with cerebral hemisphere lesions than with spinal lesions. We conclude that psychogenic limb weakness is associated with normal MEP. However, normal MEP in mildly paretic muscles do not definitely exclude organic pathology.
Adolescent↗