Abnormal reorganization in focal hand dystonia--sensory and motor training programs to retrain cortical function.

Dystonia is a disabling movement disorder, which is characterized by an abnormal pattern of muscle activity with co-contraction of agonist and antagonist muscles. In the case of focal hand dystonia (FHD), these abnormal movements affect muscles of the forearm and hand while performing a specific task. Patients may initially present with dystonic symptoms occurring with a selective task (simple writer's cramp or musician's cramp), and may progress to develop symptoms with multiple tasks (dystonic writer's cramp). The underlying cause of this disabling condition remains unclear. This review examines recent studies designed to further elucidate the underlying pathophysiological processes in focal dystonia. Animal research work, and neurophysiological and neuroimaging studies in humans, have identified several possible mechanisms that may contribute to the underlying pathophysiology, including impaired sensorimotor integration, motor cortex activation and surround inhibition. Pharmacological treatment for dystonia is currently suboptimal. Based on these recent pathophysiological findings, several promising and novel non-pharmacological treatment modalities have recently been developed. Attempts at modulating impaired sensorimotor integration and cortical inhibition using sensorimotor retraining, and the range of sensory training techniques recently described, are further discussed in this review.

Fatal toxic leukoencephalopathy: clinical, radiological, and necropsy findings in two patients.

BACKGROUND: Toxic leukoencephalopathy has been described with inhalation and intravenous consumption of heroin and cocaine. The clinical picture varies widely but the imaging and histological features are characteristic. Magnetic resonance imaging (MRI) typically reveals diffuse bihemispheric white matter lesions. Histologically there is extensive spongiform degeneration of the cerebral white matter. OBJECTIVE: To report two cases of fatal toxin associated leukoencephalopathy, along with detailed imaging and neuropathological studies. RESULTS: MRI revealed diffuse white matter changes. Histologically there was widespread confluent vacuolar degeneration of the deep white matter. In both cases, there was sparing of the brain stem and cerebellar white matter. There was evidence of severe and extensive axonal injury. CONCLUSIONS: This pattern of radiological involvement and histological findings has not previously been reported and may reflect the presence of a yet unidentified impurity.

Abnormalities of spatial discrimination in focal and generalized dystonia.

Sensory processing is impaired in focal hand dystonia (FHD), with most previous studies having evaluated only the symptomatic limb. The purpose of this study was to establish whether the sensory system is affected in other types of dystonias and whether the contralateral hand is also involved in FHD. We used a spatial acuity measure (Johnson-Van Boven-Phillips domes) to evaluate sensory spatial discrimination in both hands of patients with different forms of dystonias including primary generalized DYT1 dystonia (associated with a unique deletion in the DYT1 gene) (n = 13), FHD (n = 15), benign essential blepharospasm (n = 9), cervical dystonia (n = 10) and in age-matched controls. Clinical evaluation included the Fahn dystonia scale for the focal dystonia groups and the Marsden-Burke-Fahn scale for the generalized dystonia group. Spatial discrimination was normal in patients with DYT1 dystonia, despite all of these patients having hand dystonia. However, spatial discrimination thresholds were significantly increased in both hands in the focal dystonia groups (thresholds were similar for each group) and did not correlate significantly with either severity or duration of dystonic symptoms. Thresholds were significantly increased in the dominant hand compared with the non-dominant hand only within the FHD group. Our observations demonstrate involvement of both the dominant and non-dominant somatosensory cortices, and suggest that abnormal sensory processing is a fundamental disturbance in patients with focal dystonia. These findings of altered sensory processing in idiopathic focal but not generalized DYT1 dystonia suggest both a primary pathophysiological role for the phenomenon in focal dystonia and divergent pathophysiological processes in the two conditions.

Increased brainstem excitability in stiff-person syndrome.

The recovery cycle of the R2 component of the blink reflex was studied in five patients with stiff-person syndrome (SPS) and in seven healthy control subjects. R2 recovery was enhanced in patients with SPS. This result is suggestive of hyperexcitability of brainstem interneuronal circuits in SPS. Hyperexcitability may result from abnormal input from suprasegmental structures or loss of inhibition by interneurons and is compatible with the proposal that there is a widespread dysfunction of central inhibitory mechanisms in SPS.

Accuracy of muscle localization without EMG: implications for treatment of limb dystonia.

Although botulinum toxin is an effective treatment for focal dystonia, the importance of electromyography (EMG) in identifying muscles and guiding injections is unclear. The authors examined the accuracy of muscle localization in 38 muscles in patients with focal hand dystonia without EMG guidance. Only 37% of needle placement attempts reached the target muscles or muscle fascicles. This study demonstrates that EMG guidance is needed for correct localization of desired muscles.

Thalidomide neuropathy in patients treated for metastatic prostate cancer.

We prospectively evaluated thalidomide-induced neuropathy using electrodiagnostic studies. Sixty-seven men with metastatic androgen-independent prostate cancer in an open-label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3-month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection.

Bilateral painful hand-moving fingers: electrophysiological assessment of the central nervous system oscillator.

We describe a 35-year-old woman who presented with the syndrome of painful hand-moving fingers on the right side. Eight months later, she developed similar finger movements and hand discomfort on the left side. She had a history of hand trauma and recurrent shoulder dislocation on the right side. Kinesiologic electromyography suggested a common central oscillator for finger movements in both hands. Electrophysiological assessment of spinal alpha motor neuron excitability, reciprocal inhibition, and Renshaw cell inhibition failed to show any abnormalities. Somatosensory evoked potential test showed marked attenuation of N20 potential recorded from the left somatosensory cortex; paired transcortical magnetic stimulation of the left motor cortex suggested failure of cortical facilitation. The data suggest that the central oscillator responsible for finger movements is located above the spinal cord level in this patient.

Maternal Bilateral Radial Neuropathy During Childbirth in Hereditary Neuropathy With a Predisposition to Pressure Palsies (HNPP).

A 30-year-old woman developed severe bilateral radial neuropathies during vaginal delivery of twins, likely secondary to positioning and muscular effort. Subsequent evaluation led to the diagnosis of hereditary neuropathy with predisposition to pressure palsies. Avoidance of prolonged muscular effort in the arms in conjunction with medial intervention to shorten the second stage of labor may help prevent debilitating radial nerve injury in women with this disorder.