Physical therapy intervention with a low frequency of exercise for a patient with a complicated form of hereditary spastic paraplegia: a case report.

[Purpose] Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder characterized by progressive spasticity and weakness of the lower limbs. To date, the appropriate frequency and intensity of physical therapy for patients with HSP are not well-known. We created an original rehabilitation program for a patient with a complicated form of HSP, wherein the program required low-frequency involvement to adapt to the long-term insurance system in Japan. We wanted to find out whether this program could maintain the physical functions and activities of daily living (ADL) of the patient. [Participant and Methods] A 41-year-old male diagnosed with a complicated form of HSP with decreased visual acuity and ataxia of the trunk and upper limb underwent a specific rehabilitation program that included a squatting exercise, a kneeling position exercise, and a motion exercise of taking a bath. This intervention program lasted for 20 minutes per session, with a frequency of two days per week. The patient was in the program for 12 weeks. [Results] All outcome measures, including muscle strength (grip force and quadriceps) and Barthel index, remained unchanged at the end of the intervention program. [Conclusion] The original intervention program used in this study, which had a low frequency of exercise, was effective in preventing further regression of the lower limb function of the patient with a complicated form of HSP, and in preventing a decrease in the ability of the patient to perform ADL.

Reliability and validity assessment of an apathy scale for home-care patients with Parkinson's disease: a structural equation modeling analysis.

[Purpose] Based on the Starkstein Apathy Scale, an apathy scale was developed for home-care patients with Parkinson's disease using structural equation modeling (SEM), with which the data compatibility of extraction factors can be verified. [Subjects and Methods] The participants were 122 home-care patients with Parkinson's disease (mean age: 70.9 ± 7.8 years) who were member of the Aomori branch or Tohoku/Hokkaido block of the Japan Parkinson's Disease Association. A questionnaire survey (anonymous, self-administered) was carried out by distributing and collecting questionnaires by mail or a collective survey at a workshop. Construct validity was evaluated by confirmatory factor analysis using SEM. Internal consistency was investigated using Cronbach's alpha coefficient. Criterion-related validity was assessed by correlation analysis with the total score of the Beck Depression Inventory. [Results] Concerning construct validity, 11 of the 14 question items of the original scale were extracted. Cronbach's α of this scale was 0.939. For criterion-related validity, Spearman's rank correlation coefficient was 0.831. [Conclusion] The construct validity, internal consistency, and criterion-related validity of the 11-item apathy scale were confirmed. The 11-item apathy scale can serve as a useful tool for the efficient and effective assessment of rehabilitation, establishment of rehabilitation goals and programs for patients with Parkinson's disease.

Reuptake of L-DOPA-derived extracellular dopamine in the striatum with dopaminergic denervation via serotonin transporters.

The aim of our present study was to determine whether exogenous L-DOPA-derived extracellular dopamine (DA) in the denervated striatum is taken up via serotonin (5-HT) transporters. Rats with dopaminergic denervation by 6-hydroxydopamine were injected with L-DOPA 50 mg/kg (i.p.) and extracellular DA levels in the denervated striatum were measured using in vivo microdialysis technique. During the experiments, fluoxetine, a selective serotonin reuptake inhibitor, was locally perfused into the striatum through the microdialysis probe. Cumulative amounts of L-DOPA-derived extracellular DA during 300 min were increased by fluoxetine dose-dependently (10 microM and 50 microM). These results suggest that reuptake of DA via 5-HT transporters plays an important role in the clearance of L-DOPA-derived DA from the extracellular space when dopaminergic neurons are extensively denervated.

[A case of brain nocardiosis successfully treated with minocycline].

A 60-year-old man with surgically treated nocardia pyothorax was referred to our hospital since he became drowsy. Brain MRI revealed multiple brain abscesses. His cerebrospinal fluid (CSF) showed increase in polymorphonuclear cells and decrease in glucose. Since he was allergic to sulfamethoxazole * trimethoprim, ceftriaxone and then minocycline were given. Minocycline resulted in dramatic improvement of neurological symtoms, MRI findings and CSF cell count. PCR analysis of 16S ribosomal DNA using his resected thoracic wall revealed that nocardia from his tissue was strain IFM0860. Strain IFM0860 nocardia was found to be sensitive to minocycline but not to sulfamethoxazole * trimethoprim and ceftriaxone. Intravenous administration of minocycline was followed by three-year per os administration of minocycline during which he had no recurrence of brain abscess. Thus, brain nocardiosis could be successfully treated with appropriate antibiotics. The lesson from the present case is that identification of the type of nocardia by PCR analysis of 16S ribosomal DNA could help accomplish tailor-made antibiotic therapy.

A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to L-DOPA in a rodent model of Parkinson's disease.

Marked fluctuation of dopamine concentration in the striatum following long-term L-DOPA administration contributes to the development of L-DOPA-induced motor complications including L-DOPA-induced dyskinesias and wearing-off in patients with Parkinson's disease. We have shown that pretreatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A (5-hydroxytryptamine) receptor agonist, alleviates fluctuation of dopamine levels in the dopamine-denervated striatum of 6-hydroxydopamine-lesioned (hemiparkinsonian) rats after L-DOPA treatment. To determine whether co-administration of 8-OH-DPAT with L-DOPA prevents L-DOPA-induced motor complications, we examined rotation behavior and levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the striatum of 6-hydroxydopamine-lesioned rats treated with L-DOPA alone or L-DOPA + 8-OH-DPAT, twice daily, for 2 weeks. Co-administration of 8-OH-DPAT inhibited an increase of rotation behavior to L-DOPA and L-DOPA-induced increases in levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the dopamine-denervated striatum, both of which are established indices of L-DOPA-induced motor complications. These results suggest that pharmaceutical products that stimulate 5-HT1A receptors could prove useful in prevention of the development of L-DOPA-induced motor complications in patients with Parkinson's disease.

Serotonergic hyperinnervation into the dopaminergic denervated striatum compensates for dopamine conversion from exogenously administered l-DOPA.

The aim of this study was to determine whether raphe-striatal serotonergic neurons of adult rats with extensive nigro-striatal dopaminergic denervation are induced by injection of exogenous L-DOPA to contain dopamine. Double-labeling immunofluorescence study was conducted. In the lesioned striatum of rats that received L-DOPA, serotonergic hyperinnervation was observed, and dopamine was detected in serotonergic varicose fibers. These findings suggest that striatal serotonergic hyperinnervation can compensate for the lost function of dopaminergic neurons.

Amantadine increases L-DOPA-derived extracellular dopamine in the striatum of 6-hydroxydopamine-lesioned rats.

We investigated the effect of amantadine on L-DOPA-derived extracellular dopamine (DA) levels and aromatic L-amino acid decarboxylase (AADC) activity in the striatum of rats with nigrostriatal dopaminergic denervation by 6-hydroxydopamine (6-OHDA). Pretreatment with 30 mg/kg amantadine increased the cumulative amount of extracellular DA in the striatum of 6-OHDA-lesioned rats treated with 10 mg/kg benserazide and 50 mg/kg L-DOPA to 250% of that without amantadine (P<0.01). Under pretreatment with 10 mg/kg benserazide, AADC activity after 30 mg/kg amantadine administration was reduced to 43% of controls (P<0.01). Amantadine-induced increase in L-DOPA-derived extracellular DA provides the basis for the clinical usefulness of amantadine in combination with L-DOPA. However, the effect of amantadine on L-DOPA-derived extracellular DA may not be caused by changes in AADC activity.

Rapid induction of serotonergic hyperinnervation in the adult rat striatum with extensive dopaminergic denervation.

The aim of our study was to determine whether serotonergic hyperinnervation is rapidly induced in the striatum of adult rats with extensive dopaminergic denervation. Immunohistochemical study was performed on the brain sections obtained at 2 and 8 weeks after injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The extent of dopaminergic denervation was evaluated as a percentage loss of tyrosine hydroxylase immunopositive neurons in the substantia nigra pars compacta. The immunopositive areas for serotonin (5-HT) in the striatum were measured. In the lesioned rats 97.5+/-0.6% of dopamine neurons were lost. 5-HT immunopositive areas in the striatum were significantly increased both at 2 and 8 weeks after 6-OHDA injection (P<0.01). These results suggest that extensive dopaminergic denervation in adult rats induces rapid serotonergic hyperinnervation in the striatum as early as 2 weeks after lesioning.

Acute cholecystitis and duodenitis associated with Churg-Strauss syndrome.

We describe a patient with acute cholecystitis and duodenitis associated with Churg-Strauss syndrome. A 36-year-old male, who had been healthy, had abdominal pain following high fever. He had marked hypereosinophilia of 17,000/mm3. Radiographs of the chest disclosed a transient infiltrated lesion in the left lower lung. Ultrasonographic and gastroendoscopic examinations revealed acute cholecystitis and duodenitis, respectively. Endoscopic retrograde cholangiopancreatography demonstrated a filling defect suspecting aberrant ascariasis in the common bile duct. The patient suddenly developed distally dominant mononeuritis multiplex, especially in the upper limbs. Muscle biopsy revealed vasculitis of intramuscular arteries with infiltration of eosinophils. These findings fulfilled the diagnostic criteria of Churg-Strauss syndrome. Corticosteroid dramatically resolved the abdominal symptoms. Cholecystectomy and removal of the foreign body were performed. Histological examinations revealed that necrosis of the gallbladder was caused by occlusion due to thrombosed arteries and that the foreign body in the common bile duct was an aggregate of necrotic epithelium of the bile duct wall surrounded by inflammatory cells. Although abdominal complaints rarely appeared as an initial symptom in the patients with Churg-Strauss syndrome, this syndrome should be taken into consideration for an accurate diagnosis when the patients with abdominal pain of unknown origin had eosinophilia, asthma, or allergic rhinitis.

[Tandospirone citrate, a selective 5-HT1A agonist, alleviates L-DOPA-induced dyskinesia in patients with Parkinson's disease].

A rapid and excessive increase in extracellular dopamine(DA) after L-DOPA administration is considered one of the major causes for L-DOPA-induced peak-dose dyskinesia. Therefore, inhibition of excessive rise in L-DOPA-derived DA is likely to be an ideal treatment for L-DOPA-induced dyskinesia. Based on our previous experimental studies that 8-OH-DPAT, a potent 5-HT1A agonist, attenuates an increase in L-DOPA-induced extracellular DA in the striatum of the rat model of Parkinson's disease, we hypothesized that L-DOPA-induced dyskinesia in patients with Parkinson's disease is alleviated by a 5-HT1A agonist. In the present study, we administered tandospirone citrate, a selective 5-HT1A agonist, to patients with Parkinson's disease suffering from L-DOPA-induced dyskinesia. Tandospirone(15-60 mg/day) was administered to 10 patients with L-DOPA-induced peak-dose dyskinesia. Twelve weeks after tandospirone treatment, duration of dyskinesia, subjective and objective severity of dyskinesia, and parkinsonian features were evaluated. Severity of dyskinesia was decreased in 5 patients; among these, 3 patients experienced slight worsening of parkinsonian features. Four patients showed no change in dyskinesia; among these, 2 patients showed worsening of parkinsonian features. One patient had slight worsening of dyskinesia without any change in parkinsonian features. The present study demonstrated that tandospirone is effective in alleviating L-DOPA-induced dyskinesia in 50% of the patients. However, at the same time 50% patients showed slight worsening of parkinsonian features. Both the anti-dyskinetic effect and the worsening of parkinsonian features are thought to be induced by tandospirone's potent 5-HT1A agonistic activity. Diverse effect of tandospirone may be caused by its partial agonist activity on 5-HT1A receptors, or may indicate that other causes for the expression of dyskinesia exist apart from excessive rise in brain DA levels. Administration of a 5-HT1A agonist is a choice for patients with dyskinesia if the care is taken so as not to induce worsening of parkinsonian features. Further studies such as double-blind trials are needed to confirm the usefulness of a 5-HT1A agonist for L-DOPA-induced dyskinesia.

Prevalence of autosomal dominant cerebellar ataxia in Aomori, the northernmost prefecture of Honshu, Japan.

OBJECTIVE: The frequency of autosomal dominant cerebellar ataxia (ADCA) varies between different regions of Japan. This is the first report on the prevalence of ADCA subtypes in Aomori, Japan. METHODS AND PATIENTS: Sixty-five familial spinocerebellar ataxia (SCA) patients and 15 sporadic SCA patients were genetically examined. For only the SCA2 patients (n = 8), the magnetic resonance imaging (MRI) data were analyzed in detail. RESULTS: Spinocerebellar ataxia (SCA) type 6 was often observed (77.7% of cases), with SCA2 (10.6% of cases) being the next most common form. In contrast, only one of the eighty patients had SCA1. Among the 15 sporadic SCA patients, genetic mutations for SCA2, SCA6, SCA17, and SCA31 were identified, indicating that ADCAs should be considered in sporadic cases of ataxia. Furthermore, in SCA2 cases, brainstem atrophy, pontine midline linear hyperintensity, and atrophy of the frontal lobes were frequently observed using MRI. CONCLUSION: The present data indicate that the prevalence of ADCA in Aomori differs from other prefectures in the Tohoku District. MRI findings are very similar between SCA2 and multiple system atrophy (MSA), and thus care must be taken to prevent the misdiagnosis of sporadic SCA2 as MSA.

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 Parkinson's disease.

Effects of benserazide on L-DOPA-derived extracellular dopamine levels and aromatic L-amino acid decarboxylase activity in the striatum of 6-hydroxydopamine-lesioned rats.

Benserazide is commonly used for Parkinson's disease in combination with L-DOPA as a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor. However, recent studies using intact animals indicate that benserazide acts also in the central nervous system. We determined the influence of benserazide on the central AADC activity in rats with dopaminergic denervation and observed changes in extracellular dopamine (DA) levels after benserazide and L-DOPA administration. First, using in vivo microdialysis technique, we measured extracellular DA levels in the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats treated with benserazide and L-DOPA. Second, we measured AADC activity in the striatal tissues after benserazide administration. Although administration of 5, 10 and 50 mg/kg benserazide to 6-OHDA-lesioned rats showed an identical increase in exogenous L-DOPA-derived extracellular DA levels, the time to reach the peak DA levels were significantly prolonged by benserazide dose-dependently. The AADC activity in the denervated striatal tissues showed a significant decrease by 10 mg/kg and 50 mg/kg benserazide. These results suggest that benserazide reduces the central AADC activity in the striatum of rats with nigrostriatal denervation, which leads to changes in the metabolism of exogenous L-DOPA. Central activity of AADC inhibitors should be taken into consideration when they are used both in experimental and clinical studies on Parkinson's disease.

Upregulation of striatal adenosine A2A receptor mRNA in 6-hydroxydopamine-lesioned rats intermittently treated with L-DOPA.

To determine whether the adenosine A2A receptor might play a role in L-DOPA-induced dyskinesia in Parkinson's disease, we analyzed changes in the expression of A2A receptor mRNA in response to intermittent treatment with L-DOPA in rats with dopaminergic denervation by 6-hydroxydopamine (OHDA) infusion into the medial forebrain bundle. Intermittent treatment with L-DOPA increased A2A receptor mRNA levels in the dopamine-depleted striatum of 6-OHDA-lesioned rats exhibiting behavioral sensitization to L-DOPA. These results suggest that A2A receptor activation is associated with the development of motor complications induced by L-DOPA treatment.