Impaired pain processing in Parkinson's disease and its relative association with the sense of smell.

BACKGROUND AND PURPOSE: Many non-motor symptoms are associated with Parkinson's disease (PD). Of these, pain and olfactory disturbance tend to be common premotor symptoms. PD has been shown to exhibit abnormal central pain processing, although underlying mechanisms are not yet fully understood. In order to investigate this further, we assessed PD patients by specific Aδ stimulation with intra-epidermal needle electrode and determined olfactory function. METHODS: Forty-two patients (18 males and 24 females) with PD and 17 healthy control subjects (8 males and 9 females) were studied. A thin needle electrode was used to stimulate epidermal Aδ fibers, and somatosensory evoked potentials (SEPs) recorded at the vertex. Olfactory function was evaluated using the Odor Stick Identification Test for Japanese (OSIT-J) and its relationship with pain-related SEPs was investigated. RESULTS: There were no significant differences in N1 latencies or P1 latencies although N1/P1 peak-to-peak amplitudes were significantly lower (p < 0.01) in PD patients than in control subjects. In PD patients, there were significant correlations between N1/P1 amplitudes and disease duration (r = -0.35, p < 0.05), Hoehn-Yahr stage (r = -0.38, p < 0.05) and UPDRS part III (r = -0.42, p < 0.01). Furthermore, the OSIT-J scores correlated with SEP amplitude (r = 0.41, p < 0.01). CONCLUSION: Pain processing in PD patients was impaired under specific nociceptive stimulation of Aδ fibers and significant correlation with smell dysfunction was detected. We suggest that this mechanism may involve the limbic system during PD pathology.

The significance of folate deficiency in alcoholic and nutritional neuropathies: analysis of a case.

OBJECTIVE: To elucidate the significance of folate deficiency in alcoholic and nutritional neuropathies. METHODS: We preformed a comprehensive clinical screening of a patient with chronic alcoholism who manifested neuropathy, macrocytic anemia, liver dysfunction, and folate deficiency. RESULTS: A 33-y-old woman with chronic alcoholism presented with acutely progressive glove- and stocking-type sensorimotor polyneuropathy. Although an episode of neuropathy preceded the current episode by 2 y, its cause was never determined. The findings of nerve conduction studies were indicative of axonal neuropathy. Laboratory findings revealed macrocytic anemia and liver dysfunction. Her serum level of folate was reduced, whereas thiamine, riboflavin, and cobalamin levels were within normal range. The neuropathy and anemia showed gradual recovery after the initiation of folic acid supplementation. CONCLUSIONS: This case study indicates that folate deficiency should be monitored closely in patients with chronic alcoholism and associated malnutrition. Additionally, folate deficiency should be considered as a differential diagnosis of neuropathy.

Discrimination of spinal and bulbar muscular atrophy from amyotrophic lateral sclerosis using sensory nerve action potentials.

INTRODUCTION: Spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) are motor neuron diseases. Sensory impairment is sometimes observed, and electrophysiological involvement has been described in the sensory nerves of SBMA patients. We hypothesized that a sensory nerve conduction study (NCS) could be used to discriminate SBMA from ALS. METHODS: We compared the results from NCSs in a total of 120 SBMA cases confirmed by genetic analysis, 188 ALS cases, and 50 normal subjects. RESULTS: Sensory nerve action potential (SNAP) amplitudes of the SBMA group were significantly lower than in the ALS and control groups. In addition, receiver-operating characteristic curve analysis for SNAP amplitude showed that a cut-off value of 13.8 µV for median, 10.7 µV for ulnar, and 9.9 µV for sural nerve best discriminated SBMA from ALS. CONCLUSIONS: The specific decrease of SNAP amplitude in SBMA provides another useful tool for the differential diagnosis of motor neuron diseases.

Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinson's disease?

Patients with Parkinson's disease often complain of fatigue, and although cardiac sympathetic denervation is thought to be associated with fatigue, this link remains unclear. Previously, we detected cardiac sympathetic denervation in patients with Parkinson's disease using dobutamine, a selective beta-1 stimulant. To clarify the involvement of autonomic dysfunction in fatigue in Parkinson's disease, we conducted autonomic function tests on 33 patients with Parkinson's disease (mean age, 66.1 ± 5.6 years; 20 men, 13 women) and evaluated their relationships to fatigue. We divided patients into 2 groups, fatigued (n = 12) and nonfatigued (n = 21), based on an average score ≥ 3.3 on the Parkinson fatigue scale. Autonomic function tests included the coefficient of variation of R-R intervals, head-up tilt test, norepinephrine and dobutamine infusion tests, and cardiac (123) I-metaiodobenzylguanidine scintigraphy. The coefficient of variation of R-R intervals and the systolic blood pressure changes accompanying the head-up tilt test did not show significant differences between the 2 groups; however, the pressor responses in the norepinephrine and dobutamine infusion tests were significantly greater in the fatigued group than in the nonfatigued group. The (123) I-metaiodobenzylguanidine heart-to-mediastinal uptake ratio was lower in the fatigued group than in the nonfatigued group. Partial correlation analyses, using disease duration and Hoehn and Yahr stage as control variables, also demonstrated significant correlations between the Parkinson fatigue scale score and the results of the autonomic function tests and cardiac (123) I-metaiodobenzylguanidine uptake. Our results suggest that autonomic dysfunction, including cardiac sympathetic denervation, is associated with fatigue in patients with Parkinson's disease.

Urinary 8-hydroxydeoxyguanosine correlate with hallucinations rather than motor symptoms in Parkinson's disease.

BACKGROUND: Oxidative stress is causally associated with the pathogenesis of Parkinson's disease (PD). Oxygen generates a large amount of reactive oxygen species (ROS). ROS including hydroxyl radicals and H(2)O(2) react with guanine residues in DNA and produce 8-hydroxydeoxyguanosine (8-OHdG). 8-OHdG serves as a biomarker for oxidative stress in various diseases. METHOD: We investigated urinary 8-OHdG levels in 61 PD patients and 28 normal subjects to evaluate the correlation with various clinical features. We quantified disease severity using the Unified Parkinson's Disease Rating Scale for motor symptoms (UPDRS part 3), the Mini-Mental State Examination (MMSE) for mental function, and the Tottori University Hallucination Rating Scale (TUHARS) for quantifying hallucinations. RESULTS: There were significant correlations between 8-OHdG and all the examined parameters, but the partial correlation coefficients excluding contributions of all the other parameters showed that only TUHARS and UPDRS part 3 are significantly related to 8-OHdG. In particular, TUHARS correlates best with urinary 8-OHdG levels. CONCLUSION: The significant correlation between urinary 8-OHdG levels and hallucinations but not with dementia suggests that hallucinations are likely to have unique but unidentified mechanisms that lead to excessive production of 8-OHdG.

Lowered cardiac sympathetic nerve performance in response to exercise in Parkinson's disease.

We examined whether cardiac sympathetic denervation influences the cardiovascular response to exercise in Parkinson's disease (PD). Sixteen patients with PD were divided into two groups, according to their cardiac uptake of (123)I-metaiodobenzylguanidine (denervated group, 10 patients with heart to mediastinum (H/M) ratio < 1.7; innervated group, six patients with H/M ratio > 1.7) and compared changes in blood pressure (BP), heart rate (HR), and cardiac contractility with 13 control subjects during ergometric exercise stress. Velocity index (VI), an indicator of cardiac contractility, was measured using impedance cardiography and recorded every minute. Exercise began at a power output of 20 W for the first 2 min and increased 10 W every 2 min to a maximal intensity of 60 W. All control subjects accomplished the procedure while six patients with PD could not continue after the first minute of 50 W loading. There were no significant differences in BP or HR change between the three groups. However, a significant reduction in VI was observed from the first minute of the 30 W workload in the denervated group compared to the control group. This lowered response continued till 50 W loading and was significantly different to the innervated group at 50 W loading. No significant VI changes were observed between the control and innervated groups throughout the exercise test. Patients with PD with reduced MIBG uptake had a lowered cardiac contractility than innervated subjects during exercise, suggesting that this response represents the impaired exercise capacity of patients with PD with cardiac sympathetic denervation.

The profile of motor unit number estimation (MUNE) in spinal and bulbar muscular atrophy.

OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is a lower motor neuron disease caused by the expansion of a trinucleotide CAG repeat in the androgen receptor (AR) gene. The fundamental histopathological finding of this disease is an extensive loss of lower motor neurons in the spinal cord and brainstem. It is, however, difficult to evaluate clinically the degree of motor neuron degeneration, which stresses the need for biomarkers to detect the remaining neuronal function. METHODS: The authors performed motor unit number estimation (MUNE) in 52 patients with SBMA, to investigate whether this method could be a potential biomarker of SBMA, and re-evaluated MUNE 1 year later in a subgroup of the patients. RESULTS: The number of functioning motor units was remarkably reduced in patients with SBMA compared with controls, and was correlated with both ipsilateral grip power and disease duration. A longitudinal analysis demonstrated a further reduction in motor units within 1 year. CONCLUSIONS: The results suggest that MUNE is an electrophysiological parameter that reflects the severity and progression of motor neuron degeneration in patients with SBMA.

An autopsied case of panencephalopathic-type Creutzfeldt-Jakob disease with mutation in the prion protein gene at codon 232 and type 1 prion protein.

In this study, we describe the clinicopathologic findings in a 68-year-old man with panencephalopathic-type CJD with a substitution from methionine to arginine at codon 232 (M232R) in the prion protein (PrP) gene and type 1 PrP. Initial symptoms of the patient were a rapidly progressive memory disturbance and disorientation. The patient showed myoclonus and periodic sharp-wave complexes on electroencephalogram in the early stages of disease. Diffusion-weighted MRI along with the presence of both neuron-specific enolase and 14-3-3 protein in the CSF showed similarities to classic-type sporadic CJD. The patient reached the akinetic mutism state 2 months following the onset of symptoms and died after 13 months. Neuropathologic examination revealed panencephalopathic-type CJD pathology including widespread neuron loss with severe hypertrophic astrocytosis and status spongiosus in the cerebral gray matter, particularly in the neocortex. Cerebral white matter and the cerebellum also showed severe involvement. Immunohistochemical staining for PrP showed diffuse gray matter staining, indicating synaptic-type PrP deposition without plaque-type. Two different clinical phenotypes of M232R CJD were recognized despite the presence of the same PrP genotype, and the present case is speculated to correspond to the rapid-type.

[Successful outcome of VP shunt operation in 3 cases of idiopathic normal pressure hydrocephalus with long duration of illness].

Three cases (70- and 83-year-old females and 77-year-old male) with cognitive impairment, gait disturbance and urinary incontinence for 8 to 15 years were diagnosed as idiopathic normal pressure hydrocephalus (iNPH) according to the iNPH guideline in Japan (2004). All were operated by ventriculo-peritoneal shunt and had a good outcome despite their long duration of illness. Two of the three cases had been earlier diagnosed as progressive supranuclear palsy (PSP). because they had vertical gaze palsy. Some iNPH patients with vertical gaze palsy clinically might be misdiagnosed as PSP.