Chieko Suzuki

Clinical availability of skin biopsy in the diagnosis of Parkinson's disease

To determine whether skin biopsy is practically useful in the premortem diagnosis for Parkinsons disease (PD), we examined Lewy pathology in the skin of the chest wall and leg, obtained from 6-mm punch biopsies, using phosphorylated alpha-synuclein antibody in 20 patients with clinically diagnosed PD. Abnormal accumulation of alpha-synuclein was found in the chest skin of two (10%) of 20 patients, but not in the leg. Although skin biopsy combined with a conventional immunohistochemistry for alpha-synuclein is not sufficient as a diagnostic tool, we could firstly demonstrate Lewy pathology in premortem tissue. The skin remains to be a promising tissue to be examined for the premortem diagnosis of PD.

High frequency oscillations in early cortical somatosensory evoked potentials

OBJECTIVE To evaluate the characteristics of high frequency (HF) components of the early cortical somatosensory evoked potentials (SEPs). METHODS We recorded 8-channel SEPs from the frontal and left centro-parietal scalp after right median nerve stimulation with a wide band-pass (0.5-2000 Hz) and digitized at 40 kHz sampling rate in 12 healthy subjects. HF components were analyzed after digital band-pass filtering (300-1000 Hz). The power spectrum was obtained by a maximum entropy method. RESULTS HF oscillations (maximum power at 600-800 Hz) consisting of 5 to 8 peaks were discriminated from the preceding P14 far-field in all cases and their phases were reversed between the frontal and contralateral parietal regions. In addition, in subjects with a high amplitude central P22 potential in original wide-band recordings, a single HF oscillation with a maximum at the central region was present. Furthermore, this component showed no phase reversal over the centro-parietal area. CONCLUSION We therefore conclude that HF oscillations are superimposed not only on the tangential N20-P20 but on the radial P22 potential, and are generated from both tangential (area 3b) and radial (area 1) current sources.

Peripheral and central conduction abnormalities in diabetes mellitus

Objectives: To investigate peripheral and central somatosensory conduction in patients with diabetes. Methods: The authors recorded sensory nerve action potentials and 5-channel somatosensory evoked potentials (SEPs) with noncephalic reference after median nerve stimulation in 55 patients with diabetes and 41 age- and height-matched normal subjects. The authors determined onset or peak latencies of the Erb’s potential (N9) and the spinal N13-P13 and the cortical N20-P20 components, and obtained the central conduction time (CCT) by onset-to-onset and peak-to-peak measurements. Results: Both onset and peak latencies of all SEP components were prolonged in patients with diabetes. The mean onset CCT in the diabetic group was 6.3 ± 0.5 msec (mean ± SD)—significantly longer than that in the control group (6.1 ± 0.2 msec)—whereas no significant difference was found in the peak CCT. The amplitudes of N9 and N13-P13 components (but not N20-P20) were significantly smaller in the diabetic group. The peripheral sensory conduction velocity was also decreased in the diabetic group, but there was no significant correlation between peripheral conduction slowing and the onset of CCT prolongation. Conclusions: Diabetes affects conductive function in the central as well as peripheral somatosensory pathways. The CCT abnormality does not coincide with lowering of the peripheral sensory conduction. The current results do not favor a hypothesis that a central–peripheral distal axonopathy plays an important role in development of diabetic polyneuropathy.

Reuptake of L-DOPA-derived extracellular DA in the striatum of a rodent model of Parkinson's disease via norepinephrine transporter.

To determine the role of norepinephrine transporter in reuptake of L‐DOPA‐derived extracellular DA in the DA‐denervated Parkinsonian striatum, we examined extracellular DA levels in the striatum of 6‐hydroxyDA‐lesioned rats that received L‐DOPA (50 mg/kg with 12.5 mg/kg of benserazide) and L‐DOPA plus desipramine (25 mg/kg), a selective norepinephrine reuptake inhibitor, using in vivo microdialysis. The pretreatment with desipramine increased levels of extracellular DA derived from administrated L‐DOPA in the DA‐denervated striatum. This study provides evidence that L‐DOPA‐derived DA is taken up by the norepinephrine transporter, instead of the dopamine transporter, in the striatum with dopaminergic denervation. This result suggests that the norepinephrine transporter could be a promising target in the treatment for Parkinsons disease. Synapse 62:632–635, 2008.

Morphologic changes of dendritic spines of striatal neurons in the levodopa-induced dyskinesia model.

Maladaptive plasticity at corticostriatal synapses plays an important role in the development of levodopa‐induced dyskinesia. Recently, it has been shown that synaptic plasticity is closely linked to morphologic changes of dendritic spines. To evaluate morphologic changes of dendritic spines of two types of striatal medium spiny neurons, which project to the internal segment of globus pallidus or the external segment of globus pallidus, in the levodopa‐induced dyskinesia model, we used 6‐hydroxydopamine‐lesioned rats chronically treated with levodopa. Dendritic spines were decreased and became enlarged in the direct pathway neurons of the model of levodopa‐induced dyskinesia. The same levodopa treatment to normal rats, in which no dyskinesia was observed, also induced enlargement of dendritic spines, but not a decrease in density of spines in the direct pathway neurons. These results suggest that a loss and enlargement of dendritic spines in the direct pathway neurons plays important roles in the development of levodopa‐induced dyskinesia.

Clinical Utility of Skin Biopsy in Differentiating between Parkinson’s Disease and Multiple System Atrophy

Background. It is often difficult to differentiate Parkinsons disease (PD) from multiple system atrophy (MSA), especially in their early stages. Objectives. To examine the clinical utility of histopathological analysis of biopsied skin from the chest wall and/or leg in differentiating between the two diseases. Methods. Skin biopsies from the lower leg and/or anterior chest wall were obtained from 38 patients with idiopathic PD (26 treated with levodopa and 12 levodopa-naïve) and 13 age-matched patients with MSA. We sought aggregates of phosphorylated α-synuclein on cutaneous nerve fibers using double fluorescence immunohistochemistry and confocal microscopy and measured intraepidermal nerve fiber density (IENFD). Results. Phosphorylated α-synuclein aggregates were identified on cutaneous nerves in two patients with PD (5.3%) but in none of the patients with MSA, and IENFD was significantly lower in patients with PD when compared to those with MSA. There was no difference in IENFD between levodopa-treated and levodopa-naïve patients with PD. Conclusions. Our findings suggest that an assessment of IENFD in biopsied skin could be a useful means of differentiating between PD and MSA but that detection of α-synuclein aggregates on cutaneous nerves in the distal sites of the body is insufficiently sensitive.

Middle Cerebellar Peduncles and Pontine T2 Hypointensities in ARSACS

Magnetic resonance imaging (MRI) of autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) cases in Quebec and Europe was reported to show linear hypointensities in T2‐weighted and Fluid Attenuated Inversion Recovery (FLAIR) images of the pons. We attempted to clarify the characteristics of the brain MRI findings in ARSACS cases.

Disseminated intraparenchymal microgranulomas in the brainstem in central nervous system sarcoidosis

We report a 70‐year‐old woman with sarcoidosis and multiple cranial nerve palsy. The patient suffered from dysarthria, dysphagia and weakness of the upper and lower extremities and died of sepsis. No abnormalities were noted in brain MRI. At autopsy, numerous epithelioid granulomas with Langhans giant cells were present in the bilateral lungs, including the hilar lymph nodes. The brain had a normal external appearance. Histologically, there were brainstem parenchymal lesions consisting of many microgranulomas, lymphocytic infiltration, activated microglias and astrocytosis. Perivascular lympocytic cuffing was also seen. Neither granulomas nor lymphocytic infiltration were seen in the leptomeninges. The present case was considered to be a peculiar type of neurosarcoidosis, that is, “sarcoid brainstem encephalitis”.

Reversible multifocal conduction block in sarcoid neuropathy.

Dear Editor, Sarcoid neuropathy has features of axonal abnormalities, either pathologically or neurophysiologically (Oh, 1980; Nemni et al., 1981; Galassi et al., 1984; Gainsborough et al., 1991; Said et al., 2002). We report two consecutive patients with sarcoid neuropathy in which nerve conduction study (NCS) revealed reversible multifocal conduction block, indicating treatable demyelinating process. Patient 1: In April 1997, a 74-year-old woman developed right facial palsy. Two months later she showed left facial palsy, left blephaloptosis, and numbness in distal extremities. Dysesthetic pain then occurred in the feet. On examination, ankle dorsoflexion, wrist extension, and the small hand muscles were weak bilaterally. Tendon reflexes were lost. Plantar responses were flexor. Vibratory sense was slightly decreased in the feet. Ophthalmologic examination revealed active iritis and bilateral chronic glaucoma. Serum lysozyme was 18 mg/mL (normal, 3.0–10.6). Autoantibodies were negative. Her blood count, electrolytes, calcium, and angiotensin-converting enzyme (ACE) were normal. Cerebrospinal fluid (CSF) protein was 71 mg/dL with no pleocytosis. Chest X-ray revealed mediastinal lymphadenopathy. Magnetic resonance imaging of brain showed no abnormalities. NCS performed on July 8, 1997 revealed the right median compound muscle action potential (CMAP) of 1.8 mV after elbow stimulation, while wrist stimulation elicited 6.3 mV CMAP. Motor conduction velocity (MCV) was 39 m/s. Left median nerve study also demonstrated abnormal amplitude reduction more than 80% after proximal stimulation (Fig. 1A). The sural compound sensory nerve action potential (CSAP) could not be elicited bilaterally. On July 15, the right median study revealed a decrease in distal CMAP with prolonged distal latency. The left median nerve showed a marked reduction in proximal amplitude to 1.2 mV, while distal CMAP was 5.2 mV. The right ulnar NCS revealed a novel abnormal reduction in proximal CMAP of 2.9 mV, while distal CMAP was 5.9 mV. In the end of July, abnormal amplitude reduction of proximal CMAP still persisted in several nerves (Table 1). Muscle biopsy from the anterior tibial muscle revealed numerous non-caseous granulomas composed of lymphocytes, epithelioid cells, and multinuclear giant cells, which were consistent with sarcoidosis. The biopsied sural nerve also showed a non-caseous granuloma that occupied the endoneurium of a nerve fascicle. No angiitis was observed. Myelinated fiber density was slightly reduced (5,261/ mm). There were some degenerating axons, clustering of small fibers, and occasional thinly myelinated fibers. We treated the patient with prednisone 30 mg/ day. Gradual symptomatic improvement developed over the next 6 months. Follow-up NCS on January 27,

A family with IVIg-responsive Charcot–Marie–Tooth disease

We report a family of intravenous immunoglobulin (IVIg)-responsive X-linked Charcot–Marie–Tooth disease Type 1 (CMT1X) with a novel gap junction protein 1 mutation. Two of three siblings in the family complained of subacute motor and sensory impairment, and their symptoms improved after the administration of IVIg. Additional IVIg treatment also resulted in similar improvement. The other also showed a mild improvement on IVIg. It has been suggested that an immune-mediated process is involved in the progression of neuropathy in CMT1X. The finding in our report provides evidence of susceptibility to immune-mediated demyelinating neuropathy in some form of CMT1X. Superimposed demyelinating neuropathy as well as a gradual deterioration of neuropathy over decades can be a clinical manifestation of CMT1X.