Karlheinz Reiners

Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography

Article abstract-To detect morphologic abnormalities in Parkinsons disease (PD), we examined 30 patients with PD and 30 age- and sex-matched nonparkisonian controls by transcranial color-coded real-time sonography (TCCS). In 12 severely affected PD patients, the echogenicity of the substantia nigra was distinctly increased. In the remaining 18 PD patients and in all controls, the substantia nigra was poorly visualized or nondetectable by TCCS. The degree of hyperechogenicity of the substania nigra closely correlated with the severity and duration of PD (p < 0.001). The increased echogenicity of the substania nigra notably results from nigral gliosis and reflects the stage of degeneration. NEUROLOGY 1995;45: 182-184

Vulnerability of the nigrostriatal system as detected by transcranial ultrasound

Objective: To assess the incidence of a hyperechogenic substantia nigra (SN) by transcranial sonography (TCS) in healthy people and to evaluate whether an enlarged hyperechogenic SN area is associated with functional impairment of the nigrostriatal system. Background and Methods: Until now, preclinical impairment of the nigrostriatal system could be identified only by functional neuroimaging techniques such as PET in selected groups of patients. TCS is a new, noninvasive ultrasound technique that has demonstrated an increased echogenicity of the SN in patients with PD, whereas in most healthy individuals, the SN is either barely detectable or undetectable by TCS. Results: Of 330 healthy volunteers, 8.6% exhibited an increased echogenicity of the SN. From these, 10 clinically healthy individuals with distinct unilateral or bilateral hyperechogenic signals in the SN region (SN area above 0.25 cm2) underwent comprehensive motor testing, neuropsychological assessment, MRI, and [18F]-dopa PET examination. With regard to motor functions, these individuals did not differ from 10 age- and sex-matched controls with a low echogenic SN and an area of echogenic signals below 0.2 cm2. Enlargement of hyperechogenic areas in the 10 healthy individuals was associated with a marked decrease in the accumulation of [18F]-dopa in the caudate nucleus and putamen. Conclusions: Substantia nigra hyperechogenicity appears to indicate a functional impairment of the nigrostriatal system. Transcranial sonography may be a suitable method of identifying persons at risk of nigrostriatal alterations, making possible the introduction of early neuroprotective therapy.

Five-year follow-up study of hyperechogenicity of the substantia nigra in Parkinson's disease

Using transcranial sonography, an area of hyperechogenicity at the substantia nigra (SN) may be detected as a typical marker in patients with Parkinsons disease (PD) as well as in approximately 9% of healthy subjects vulnerable to nigrostriatal impairment. In this longitudinal study, we provide evidence that the area of SN hyperechogenicity does not change in the course of PD. In conjunction with earlier findings in children and adolescents, this evidence indicates that, from late adolescence onward, this ultrasound finding is a trait marker for nigrostriatal vulnerability.

Small fibre pathology in patients with fibromyalgia syndrome

Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.

Timing-dependent plasticity in human primary somatosensory cortex

Animal experiments suggest that cortical sensory representations may be remodelled as a consequence of changing synaptic efficacy by timing‐dependent associative neuronal activity. Here we describe a timing‐based associative form of plasticity in human somatosensory cortex. Paired associative stimulation (PAS) was performed by combining repetitive median nerve stimulation with transcranial magnetic stimulation (TMS) over the contralateral postcentral region. PAS increased exclusively the amplitude of the P25 component of the median nerve‐evoked somatosensory‐evoked potential (MN‐SSEP), which is probably generated in the superficial cortical layers of area 3b. SSEP components reflecting neuronal activity in deeper cortical layers (N20 component) or subcortical regions (P14 component) remained constant. PAS‐induced enhancement of P25 amplitude displayed topographical specificity both for the recording (MN‐SSEP versus tibial nerve‐SSEP) and the stimulation (magnetic stimulation targeting somatosensory versus motor cortex) arrangements. Modulation of P25 amplitude was confined to a narrow range of interstimulus intervals (ISIs) between the MN pulse and the TMS pulse, and the sign of the modulation changed with ISIs differing by only 15 ms. The function describing the ISI dependence of PAS effects on somatosensory cortex resembled one previously observed in motor cortex, shifted by ∼7 ms. The findings suggest a simple model of modulation of excitability in human primary somatosensory cortex, possibly by mechanisms related to the spike‐timing‐dependent plasticity of neuronal synapses located in upper cortical layers.

T cell activation in Guillain‐Barré syndrome and in MS Elevated serum levels of soluble IL‐2 receptors

Guillain-Barré syndrome (GBS), chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), and multiple sclerosis (MS) are disorders with presumed immunopathogenesis. To obtain evidence for T cell activation, we determined serum concentrations of soluble interleukin-2 receptors (sIL-2 R) in 50 patients with GBS, 24 with CIDP, and 54 with MS. Both in GBS and clinically active MS sIL-2 R levels were markedly increased compared with those in patients with other neurologic diseases. Four of 24 CIDP patients had abnormally increased sIL-2 R concentrations. sIL-2 R concentrations decreased with clinical improvement in serial samples taken from GBS patients, but were not otherwise correlated with disease severity. These data establish that T cells are activated in GBS and some patients with CIDP, and corroborate earlier evidence that activated T cells are circulating in the blood of MS patients.

Sensory tricks in cervical dystonia: Perceptual dysbalance of parietal cortex modulates frontal motor programming

Cervical dystonia is a disabling basal ganglia disorder characterized by an involuntary head deviation to one side. A typical but also mysterious feature is the impressive improvement of muscle spasms and involuntary head posture by application of a sensory facial stimulus (sensory trick). Here, we report the effect of a sensory trick on cortical activation patterns in 7 patients with cervical dystonia by using H215O positron emission tomography. The application of the sensory trick stimulus, resulting in a near‐neutral head position, led to an increased activation mainly of the superior and inferior parietal lobule (ipsilateral to the original head turn) and bilateral occipital cortex and to a decreased activity of the supplementary motor area and the primary sensorimotor cortex (contralateral to the head turn). We propose that a perceptual dysbalance induced by a sensory trick maneuver leads to a relative displacement of the egocentric midvertical reference to the opposite side and a decrease in motor cortex activity. This modulation of motor programming gives novel insights into the mechanisms involved in sensorimotor integration in movement disorders. Ann Neurol 2000;47:322–328

MRI of peripheral nerve degeneration and regeneration: correlation with electrophysiology and histology

Acute axonal nerve lesions cause a hyperintense signal on T2-weighted (T2-w) magnetic resonance imaging (MRI) at the nerve lesion site and distal to it. The aim of this experimental study was to investigate the spatiotemporal evolution and resolution of MR nerve signal changes following denervation and reinnervation, and to relate these findings to electrophysiology and histology. The proximal sciatic nerve of adult rats was ligated by a tight suture that was removed 1 week later to induce complete axotomy and nerve regeneration upon release. Serial electromyography (EMG) and motor nerve conduction studies were performed parallel to MRI at multiple points of time. Moreover, sciatic nerves were taken for quantitative histological evaluation. Nerve hyperintensity on T2-w MRI was present distal to the lesion at thigh level 24 h after denervation preceding the occurrence of spontaneous activity on EMG by 24 h. After 48 h, the entire sciatic nerve and its branches showed an increased signal down to the level of the lower leg. The increased nerve signal regressed with a proximo-distal gradient beginning from week 2 after onset of nerve regeneration in the thigh. On EMG, the first reinnervation potentials were detected at that time at the respective level. Compound muscle action potential (CMAP) in the foot muscle fully recovered 12 weeks after onset of nerve regeneration, that is, 2 weeks after resolution of the hyperintensity along the entire nerve on MRI. Histology revealed axonal degeneration in the acute phase and later nerve oedema parallel to the increased nerve signal on MRI. MR signal alterations occur as early as 24 h after an axonal nerve lesion and correlate with nerve fiber degeneration and later with nerve oedema on histology. MR findings in denervation and reinnervation parallel the electrophysiological changes. Thus, MRI is a promising diagnostic tool for the early detection of acute axonal nerve lesions and monitoring of nerve regeneration.

Botulinum toxin for palmar hyperhidrosis

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Differential effects of changes in mechanical limb properties on physiological and pathological tremor.

The effect of changes in mechanical limb properties on the peak frequency of different tremor forms was analysed. Wrist tremor was recorded by an accelerometer fixed to the dorsum of the hand and demodulated surface EMG was recorded from the wrist extensors, while the extended hand was loaded with successively heavier weights. Physiological tremor was characterised by flat EMG spectra and a gradual decrease in tremor peak frequency with increasing load, as would be expected from the properties of a passive spring-mass-system. Also the peak frequency of activated physiological tremor characterised by increased synchronisation between motor units decreased in frequency with increasing loads. EMG spectra showed clear peaks of activity at the various mechanically determined tremor frequencies. In contrast, in two pathological tremor forms, the postural tremor in Parkinsonian patients and essential tremor, peak frequency tended to remain stable irrespective of changes in load. The method therefore allows a simple distinction between physiological and these two pathological tremors.