Acute Cerebellar Manifestations without Limbic Involvement in GABAB Receptor Autoimmune Encephalitis: Case Report and Literature Review.

Autoimmune encephalitis is a rapidly progressive inflammatory brain disease. Gamma-aminobutyric acid type B (GABAB) receptor autoimmune encephalitis is a rare subtype characterized by distinct clinical features. Diagnosis can be especially challenging when typical limbic symptoms and neuroimaging findings are absent. This case report underscores the importance of identifying this condition and starting immunosuppressive treatment promptly. A 59-year-old man presented with gait disturbances, dysarthria, and severe ataxia without cognitive impairment. Initial examinations, including a brain MRI, were unremarkable, except for an elevated cell count and protein in the cerebrospinal fluid. Despite receiving initial empirical antiviral treatment, his symptoms worsened, prompting the administration of intravenous methylprednisolone and immunoglobulin. After these immunosuppressive therapies, the cerebellar symptoms showed gradual improvement. Subsequent testing for antibodies to the GABAB receptor was positive in both the serum and cerebrospinal fluid. Follow-up MRI revealed cerebellar atrophy, consistent with a diagnosis of GABAB receptor-associated acute cerebellitis. This case illustrates that cerebellar symptoms can occur in the absence of more common limbic manifestations in GABAB receptor autoimmune encephalitis. The progression of cerebellar atrophy following an initially normal MRI is a significant finding that offers supporting evidence for the diagnosis of cerebellitis. A review of the literature identified similar cases of acute cerebellitis without limbic symptoms, although neuroimaging abnormalities in the cerebellum were not reported. Our case underscores the importance of increased clinical awareness and consideration of autoimmune causes, even when neuroimaging appears normal. Early and appropriate immunosuppressive therapy may help change the course of the disease and enhance patient outcomes.

Prognostic evaluation of branch atheromatous disease in the pons using carotid artery ultrasonography.

BACKGROUND: Branch atheromatous disease is an ischemic stroke, involving occlusion or severe stenosis of the perforating artery, causing neurologic symptoms and serious sequelae. We aimed to investigate initial morphometric and hemodynamic characteristics of the vertebral artery immediately post-onset to predict lesion expanding. METHODS: This case-control study collected demographic, historical, and physical examination data from 44 patients with branch atheromatous disease in the pons at admission. The maximum ischemic pons area and stenosis rate in the basilar artery were calculated using magnetic resonance images. Diameter, velocity, and flow volume of the vertebral arteries were measured using carotid artery ultrasonography. Correlations between ischemic lesion extent and these parameters were investigated. RESULTS: Patients were assigned to groups of less (Group 1) or more (Group 2) than the median maximum ischemic area in the pons, calculated from magnetic resonance images (121.6 mm2). Modified Rankin scale scores were significantly worse in Group 2. Blood pressure and blood findings were similar between groups. Group 2 showed significantly higher basilar artery stenosis rates. Flow volume, velocity, peak systolic velocity, and end-diastolic velocity in the vertebral artery on both sides were significantly decreased in Group 2. CONCLUSIONS: Deteriorated vertebral artery hemodynamics caused a more extensive ischemic lesion in branch atheromatous disease in the pons. Evaluation of the vertebral using carotid artery ultrasonography in the acute phase may be useful for predicting disease progression.

Phase II Trial of Intravenous Low-Dose Granulocyte Colony-Stimulating Factor in Acute Ischemic Stroke.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) has shown neuroprotective and neurogenerative activities in experimental studies, and our previous phase I clinical study suggested the safety and potential efficacy of low-dose G-CSF in acute ischemic stroke patients. The present phase II trial is aimed to evaluate the effect of G-CSF administration on neurological function and infarct volume, compared with a placebo group. METHODS: Forty-nine acute ischemic stroke patients (29 males, 20 females; 71 ± 10 years) within 24 hours after onset were recruited. Eligible patients were randomized 2:2:1 to receive G-CSF 150 µg/body/day, G-CSF 300 µg/body/day, and placebo, respectively. We evaluated clinical outcome in terms of the National Institutes of Health Stroke Scale, the modified Rankin Scale, and the Barthel Index at 90 days after onset, together with changes in infarct volume on magnetic resonance imaging. RESULTS: We found no serious adverse event, including change in leukocyte levels, which remained below 31,000/µL, at 150 and 300 µg G-CSF/body/day. Clinical outcome scores did not show any significant difference among the 3 groups. Chronological changes in infarct volume also showed no significant difference. CONCLUSIONS: G-CSF was well-tolerated at 150 and 300 µg/body/day in patients with acute ischemic stroke. However, administration of G-CSF at both 150 and 300 µg/body/day neither contributed to functional recovery nor reduced infarct volume at 3 months after onset, compared with the control group. The apparent lack of effectiveness may have been due to the small sample size. A trial of combination therapy with recombinant tissue plasminogen activator and G-CSF is planned.

Predictors of the emergence of apathy after bilateral stimulation of the subthalamic nucleus in patients with Parkinson's disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is a valid therapeutic tool that ameliorates motor symptoms in patients with Parkinson's disease (PD). However, apathy is one of the neuropsychiatric complications that may occur after STN-DBS surgery, and this may adversely influence the quality of life of patients despite significant motor improvement. OBJECTIVE: This study aimed to elucidate preoperative predictive factors for the presence of postoperative apathy in patients treated with STN-DBS. METHODS: Twenty-five consecutive PD patients receiving bilateral STN-DBS were recruited. The assessment instruments include modified Hoehn & Yahr stages, Unified Parkinson's Disease Rating Scale motor (part III) and dyskinesia (part IVa) scores, Parkinson's Disease Questionnaire-39 scores, Self-Rating Depression Scale scores, and Apathy Scale scores. Predictive factors for postoperative apathy were assessed. RESULTS: While STN-DBS resulted in a significant improvement in motor symptoms, six patients (24%) developed significant apathy after surgery. In multiple logistic regression analyses, preoperative severity of dyskinesia was found to be an independent predictor for the acute phase of postoperative apathy with STN-DBS (odds ratio = 89.993, p = 0.003). CONCLUSIONS: This study suggests that preoperative dyskinesia may predict postoperative apathy in the acute phase in patients with PD treated with STN-DBS. The pathogenesis of postoperative apathy remains unknown, but in patients with severe dyskinesia before STN-DBS, attention should be given to monitoring for postoperative apathy.

Takotsubo cardiomyopathy in Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM). METHODS: Clinical features and anti-ganglioside antibody between the GBS-TCM patients and 62 classical GBS patients without TCM as control patients were compared. RESULTS: Eight GBS-TCM patients were identified, in whom TCM was diagnosed at a mean of 6.5 [range 3-42] days after the onset of GBS. The age at onset of GBS was elder in the GBS-TCM patients than in the control GBS patients (76.5 [56-87] vs. 52 [20-88] years, p < 0.01). Notably, cranial nerve deficits, particularly in the lower cranial nerves, were observed in all GBS-TCM patients (100% vs. 41.9%, p < 0.01). Additionally, the GBS-TCM patients showed a higher GBS disability score at nadir (5 [4-5] vs. 4 [1-5], p < 0.01), and lower Medical Research Council sum scores at admission and nadir (37 [30-44] vs. 48 [12-60] at admission, p < 0.05, and 20 [12-44] vs. 40 [0-60] at nadir, p < 0.05, respectively). Mechanical ventilation was more frequently required in the GBS-TCM patients (62.5% vs. 11.3%, p < 0.01). Three GBS-TCM patients were positive for anti-ganglioside antibodies. CONCLUSIONS: TCM occurred at a relatively early phase of GBS. The characteristics of GBS-TCM were the elder, lower cranial nerve involvements, severe limb weakness, and respiratory failure.

Cerebral white matter lesions and regional blood flow are associated with reduced cognitive function in early-stage cognitive impairment.

Background: Differences in the extent of cerebral white matter lesions (WML) and regional cerebral blood flow (rCBF) in early-stage cognitive impairment (ESCI) contribute to the prognosis of cognitive decline; however, it is unclear precisely how WML and rCBF affect cognitive decline in ESCI. Objective: We examined the association between WML, rCBF, and cognitive impairment in the ESCI, using path analysis to clarify how these variables affect each other. Methods: Eighty-three patients who consulted our memory clinic regarding memory loss were included in this study based on the Clinical Dementia Rating. Participants underwent the Mini-Mental State Examination (MMSE), brain magnetic resonance imaging (MRI) for voxel-based morphometry analysis, and brain perfusion single-photon emission computed tomography (SPECT) for rCBF evaluation in cortical regions, using 3D stereotactic surface projection (3D-SSP) analysis. Results: Path analysis was performed on the MRI voxel-based morphometry and SPECT 3D-SSP data, showing a significant correlation between both and MMSE scores. In the most suitable model (GFI = 0.957), correlations were observed between lateral ventricular (LV-V) and periventricular WML (PvWML-V) volumes [standardized coefficient (SC) = 0.326, p = 0.005], LV-V and rCBF of the anterior cingulate gyrus (ACG-rCBF; SC = 0.395, p < 0.0001), and ACG-rCBF and PvWML-V (SC = 0.231, p = 0.041). Furthermore, a direct relationship between PvWML-V and MMSE scores was identified (SC = -0.238, p = 0.026). Conclusion: Significant interrelationships were observed among the LV-V, PvWML-V, and ACG-rCBF that directly affected the MMSE score in the ESCI. The mechanisms behind these interactions and the impact of PvWML-V on cognitive function require further investigation.

IgG index of cerebrospinal fluid can reflect pathophysiology associated with Lewy bodies in Parkinson's disease.

BACKGROUND: Neuroinflammation is one of the pathophysiologies of Parkinson's disease (PD). Lewy bodies, the pathological hallmark of PD, emerge as a consequence of α-synuclein aggregation, and neuroinflammation is induced concurrently with this aggregation. Imaging and cerebrospinal fluid (CSF) biomarkers that reflect PD pathophysiology have been developed or are under investigation. The IgG index of CSF is a marker of inflammation, and may also reflect the pathophysiology of PD. AIM: We examined if the IgG index reflects the pathophysiology of PD in drug-naïve PD patients. METHOD: The subjects were 20 consecutive PD patients who underwent 123I-MIBG scintigraphy for assessment of the heart to mediastinum (H/M) ratio and wash out rate, 123I-Ioflupane SPECT for examination of the specific binding ratio in the striatum, and lumbar puncture before treatment. The CSF IgG index and levels of pathogenic proteins (total α-synuclein, oligomeric α-synuclein, total tau, phosphorylated tau and amyloid Aß1-42) were determined. The IgG index was compared with the other parameters using Spearman correlation analysis. RESULTS: The IgG index showed a significant correlation with the H/M ratio in early (r = -0.563, p = 0.010) and delayed (r = -0.466, p = 0.038) images in 123I-MIBG scintigraphy and with the CSF total tau level (r = -0.513, p = 0.021). CONCLUSION: Neuroinflammation is involved in PD pathophysiology in some patients, and a higher IgG index indicates the presence of neuroinflammation accompanied by emergence of Lewy bodies.

The relationship between the distinct ratios of benserazide and carbidopa to levodopa and motor complications in Parkinson's disease: A retrospective cohort study.

BACKGROUND: In Japan, only two medications of immediate-release levodopa with distinct ratios of decarboxylase inhibitor (DCI), namely levodopa/benserazide 100/25 mg and levodopa/carbidopa 100/10 mg, are available for the treatment of Parkinson's disease (PD). The relationship between the difference in the DCI to levodopa ratio and the development of motor complications in long-term administration of levodopa is unknown. PURPOSE: We assessed the duration from initiation of levodopa/DCI to the emergence of motor fluctuations in patients with PD treated with levodopa/benserazide and levodopa/carbidopa. METHODS: We retrospectively assessed the disease course, especially the period from the onset of motor symptoms or initiation of levodopa/DCI to the emergence of motor fluctuations, in patients with PD who were initially treated with either levodopa/benserazide (300/75 mg/day) or levodopa/carbidopa (300/30 mg/day). RESULTS: Of the 186 candidates, 52 patients were enrolled. The mean duration to the emergence of motor fluctuations in the levodopa/carbidopa group was significantly longer than that in the levodopa/benserazide group (5.0 ± 1.4 vs 3.1 ± 1.2 years, p < 0.01). The mean duration from onset of motor symptoms to the emergence of motor fluctuations in the levodopa/carbidopa group was also significantly longer than that in the levodopa/benserazide group (6.6 ± 1.6 vs 4.7 ± 1.3 years, p < 0.01). CONCLUSION: Our study suggests that levodopa/carbidopa therapy with a DCI to levodopa ratio of 1:10 may delay the occurrence of motor fluctuations when compared to levodopa/benserazide therapy with that of 1:4. The difference in the blending ratio of levodopa/DCI may influence the disease progression in PD.

[A case of anti-aquaporin 4 antibody-positive Sjögren syndrome associated with a relapsed myelitis in pregnancy].

It is known that pregnancy influences the relapsing rate of multiple sclerosis (MS); however, interaction between pregnancy and relapse of neuromyelitis optica (NMO), a distinct disease from MS, remains unclear. A 34-year-old woman who 1 year previously had clinical history of Sjögren syndrome complicated by myelitis with the presence of anti-AQP4 antibody in her serum, although there was no optic neuritis involvement, was neurologically normal at time of becoming pregnant. In the 22nd week of her pregnancy, however, she developed abdominal belt-shaped numbness and sensory impairment followed by weakness of bilateral lower limb leading to difficulty of her gait. MR imaging revealed hyperintense lesions within the spinal cord extending from C2 to T2 vertebral level with marked spinal cord swelling, indicating relapse of myelitis associated with anti-AQP4 antibody. She was treated with intravenous corticosteroid with marked benefits for her neurological status; she was able to walk without assistance after the treatment. However, in the 30th week she relapsed with myelitis at T2 to T9 vertebral level on MR imaging. Intravenous steroid administration again elicited improvement. She delivered a baby via Caesarean section at 34 weeks of pregnancy. After delivery, she started taking oral corticosteroid as preventive therapy for further relapse of myelitis; thus far she has had no relapse at 7 months of follow-up. There are few reports regarding the influence of pregnancy on anti-AQP4 antibody-positive myelitis. Although further investigation should be done to clarify the difference of immunological changes during pregnancy between NMO and conventional MS, our case together with previous reports indicate increased risk of relapse during pregnancy in NMO. It is necessary to remain vigilant against possible risk of relapse during pregnancy in patients with NMO and/or positive anti-AQP4 antibody. Intravenous steroid administration seems safe and effective against relapse of NMO during pregnancy.

[Examination of the Relationship between Worse Symptom and Differences Route during Administration of Argatroban in Acute Ischemic Stroke Patients].

The treatment of acute ischemic stroke usually involves argatroban administration by continuous infusion for 2 d and by intravenous infusion twice a day for 5 d after that. However, the appropriate dose of argatroban to be administered is not clear. Therefore, no studies have been reported a comparison of intravenous and continuous argatroban infusion after day 3 for acute ischemic stroke patients. We aimed to identify the connection between differences in argatroban administration and worsening of symptoms after day 3 in ischemic stroke patients. We retrospectively evaluated the data of 107 ischemic stroke patients who received treatment with argatroban. The study endpoint was defined as the worsening of symptoms from days 3 to 7. Logistic regression analysis was used to determine the risk factors that were significantly associated with worsening of symptoms. Patients were administered argatroban, with rates of 72.0%, and 28.0% for continuous, and intravenous infusion, respectively. A total of 10 (9.3%) patients experienced worsening of symptoms. In the single logistic regression analysis, carotid stenosis [non-adjusted odds ratio (OR) 5.775, 95% confidence interval (CI) 1.486-22.442, p=0.011] was only significantly associated with worsening of symptoms. Worsening of symptoms was not related to either intravenous or continuous infusion group (16.7% vs. 6.5%, p=0.104). Bleeding was also not associated with either group (6.7% vs. 3.9%, p=0.618). We suggest that the differences in the mode of argatroban administration were not related to the worsening of symptoms in ischemic stroke patients. We also found that safety was equivalent regardless of the administration route.

Nonsystemic vasculitic neuropathy in a patient with IgG-monoclonal gammopathy of undetermined significance: A case report.

RATIONALE: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell proliferative disorder that consistently precedes multiple myeloma. Peripheral neuropathy in patients with IgG-MGUS tends to vary in clinical phenotype. We report a rare case of a patient with IgG-MGUS who had nonsystemic vasculitic neuropathy (NSVN). PATIENT CONCERNS: A 56-year-old Japanese woman presented with progressive sensory ataxia with episodic paresthesia. Her clinical and laboratory values were compatible with IgG-MGUS. A nerve conduction study suggested possible chronic inflammatory demyelinating polyneuropathy. However, intravenous immunoglobulin therapy was not effective. A sural nerve biopsy specimen revealed mildly reduced myelinated fiber density and myelin ovoid formation, with epineural arterioles infiltrated by inflammatory cells. DIAGNOSES: We accordingly diagnosed her condition as NSVN. INTERVENTIONS: She was accordingly started on oral prednisolone (40 mg/d) at 3 months after the onset of her neurological symptoms. OUTCOMES: At 1 year after the oral prednisolone treatment was begun, the patient's neurological symptoms showed no worsening. LESSONS: These findings indicate NSVN as a possible cause of peripheral neuropathy in patients with IgG-MGUS. Cumulatively, our findings highlight the need for a nerve biopsy for peripheral neuropathy in patients with IgG-MGUS as a possible cause of NSVN. The early diagnosis of NSVN is expected to be beneficial for such patients.

Recurrent HyperCKemia with Immunological Involvement of the Endomysial Capillaries in Neuromyelitis Optica.

A 55-year-old woman with neuromyelitis optica (NMO) had recurrent myalgias with hyperCKemia. A muscle biopsy suggested nonspecific myopathic changes. Regarding immunohistochemistry, the expression of both major histocompatibility complex class I and myxovirus resistance protein A was observed in the endomysial capillaries, suggesting immunological involvement of these capillaries, whereas both C5b9 (membrane attack complex) and aquaporin 4 immunofluorescence stainings were normal. The present findings led us to conclude that one possible mechanism for hyperCKemia in NMO underlying the immunological involvement of the endomysial capillaries was an as-yet-unidentified factor that triggered damage to the integrity of the sarcolemma and thereby cause CK leakage into the serum.

High serum high-density lipoprotein-cholesterol is associated with memory function and gyrification of insular and frontal opercular cortex in an elderly memory-clinic population.

The issue of whether serum lipid marker values are cognitively and neurologically significant for elderly individuals attending a memory clinic has been controversial. We investigated the associations of serum lipid markers with the memory function and cortical structure in 52 patients aged ≥75 years who had attended our memory clinic based on their subjective memory complaints. None had a history of medication for hyperlipidemia. The Wechsler Memory Scale-Revised (WMS-R) was administered to all patients for the assessment of their memory function. Serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDLC), and triglyceride (TG) were measured for each patient. Surface-based morphometry (SBM) was performed for the calculation of each patient's cortical thickness and gyrification index based on structural MRI data. Our analyses revealed that the serum HDLC level was positively and significantly correlated with the WMS-R subtests of visual paired associates I/II and logical memory I (p < 0.05). The serum TG level was negatively correlated with the logical memory I subtest. The SBM results showed positive correlations between the serum HDLC level and the gyrification indices of the bilateral insular and frontal opercular cortices, and those two gyrification indices were positively correlated with the logical memory I and visual paired associates I/II. These results suggest that in these elderly patients, a high serum HDLC level was associated with not only preserved memory function but also gyrification of the insular and frontal opercular cortex. We conclude that elderly individuals' serum lipid markers should be carefully assessed in memory clinic settings, because serum HDLC may be a biomarker for memory function and cortical structure.

ATP-binding cassette transporter G4 is highly expressed in microglia in Alzheimer's brain.

Apolipoprotein E epsilon4 is an independent risk factor for Alzheimer's disease (AD) and is the main constituent of high-density lipoprotein (HDL) as a source of cholesterol in the brain. ATP-binding cassette transporter G4 (ABCG4) is one of the membrane cholesterol transporter which is implicated in HDL-mediated cholesterol efflux, but its precise localization and function in the brain has been unclear. In AD brain, ABCG4 protein was highly expressed in microglial cell that was closely located to senile plaques, whereas in non-neurological cases positive cells were not seen in cortical and nigral tissues. As well as the ABCG4 protein, ABCG4 mRNA signal was detected in microglial cell closely located to senile plaque of AD brain by in situ hybridization histochemistry. These results suggest that upregulated ABCG4 in microglia may accelerate the lipidation of apoE and HDL in the AD brain. This is the first report to show that ABCG4 is highly expressed in microglia on AD brain.

Essential tremor: phenotypic expression in a clinical cohort.

OBJECTIVES: Examine the characteristics of an essential tremor (ET) clinical cohort including base-rate variability of several commonly accepted diagnostic criteria. METHODS: A clinical series of 487 consecutive individuals diagnosed with ET were included for study. RESULTS: The sample was 53% male, had a mean age of onset of 52, and a mean age of 71. Half of the sample had a family history of ET. Half presented with asymmetrical disease and tremor affected the arms (97%), voice (62%), and head or neck (48%). There was considerable variability in the base rate of individuals fulfilling various commonly used diagnostic criteria of ET. CONCLUSION: The sample was deemed representative of ET clinical cohorts. Asymmetric disease was common, and there was considerable base-rate variation across traditional ET diagnostic criteria.

Aprataxin (APTX) gene mutations resembling multiple system atrophy.

Mutations of the aprataxin (APTX) gene cause early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), also called ataxia with oculomotor apraxia type 1. Recent studies showed clinical heterogeneity in patients with EAOH. We describe 2 patients whose clinical features resembled those of multiple system atrophy of the cerebellar subtype (MSA-C) but without ocular motor apraxia and hypoalbuminemia. Each had a different nucleotide transition in the APTX gene (725G-->A and 457A-->G). These variants on the APTX gene exhibit phenotypic variability.

Combined use of dopamine transporter imaging (DAT-SPECT) and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy for diagnosing Parkinson's disease.

BACKGROUND: To examine whether combined use of 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) and 123I-MIBG myocardial scintigraphy (MIBG) is superior to either modality alone for diagnosing Parkinson's disease (PD). METHODS: Patients with probable PD (n=120) who underwent both DAT-SPECT and MIBG myocardial scintigraphy within short intervals were enrolled. Specific binding ratio (SBR) of DAT-SPECT images and heart-to-mediastinum (H/M) ratio of MIBG images were used as quantitative measures. We classified patients into 4 groups based on SBR value and H/M ratio, or into two groups based on the striatal asymmetry index (SAI) of DAT-SPECT, and examined the clinical features of each group. We also investigated the characteristics of SWEDDs (scans without evidence of dopaminergic deficits) patients. Finally, we calculated the sensitivity and specificity of each method and the combined method. RESULTS: SBR value was significantly correlated with both early and delayed H/M ratio values. Motor complications and hallucinations were observed at high frequency in the group with both lower SBR and H/M ratio, and hallucinations appeared in the group with larger SAI. SWEDDs were observed 8.3% of patients. The sensitivity and specificity of diagnosing PD were 91.7% and 15.0% by SBR of DAT-SPECT, 78.3% and 90.0% by H/M ratio of MIBG uptake, and 74.2% and 95.0% by the combined modalities, respectively. CONCLUSIONS: Combined use of DAT-SPECT and MIBG myocardial scintigraphy increases the specificity of PD diagnosis, and is helpful for understanding the clinical features or predicting complications.

Anhedonia and its correlation with clinical aspects in Parkinson's disease.

Anhedonia is one of the non-motor symptoms observed in the Parkinson's disease (PD). However, there is no clear relationship between anhedonia and its correlation with other symptoms of PD. The aim of this study is to evaluate the characteristics of anhedonia and its correlation with clinical aspects of PD in a relatively large cohort. We enrolled 318 patients with PD and 62 control subjects for this study. Patients and subjects were tested using the Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition for the assessment of anhedonia and depression. We also investigated the correlation among clinical aspects of PD, anhedonia, and depression in patients with PD. The Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition scores were significantly higher in patients with PD than in control subjects (p=0.03 and p=0.0006, respectively). All PD patients with anhedonia had a significantly higher score on the unified Parkinson's disease rating scale (UPDRS) parts I and II compared to PD patients without anhedonia. Additionally, all PD patients with depression scored significantly higher on UPDRS part I-IV than PD patients without depression. The patients with anhedonia and without depression had mild motor severity and their treatment was relatively low dosage. These results suggest that anhedonia and depression are slightly linked, but not the same. PD patients with only anhedonia may be closely linked apathy found in untreated early stages of PD.

Phenotypic commonalities in familial and sporadic Parkinson disease.

BACKGROUND: Parkinson disease (PD) is a clinically well-documented neurodegenerative disorder. However, the mechanism or mechanisms of its phenotypic expressions are still unknown. OBJECTIVE: To compare phenotypes by examining demographic and clinical features of patients with familial PD and sporadic PD and with or without a family history of PD. DESIGN: Historical review of patients with sporadic PD in clinic-based samples and individual patients diagnosed with PD from families whose linkage to mutations or loci has been identified. SETTING: Movement disorder clinic in a referral center. PATIENTS: A total of 1277 patients with sporadic PD and 40 patients with familial PD. MAIN OUTCOME MEASURES: Clinical features, including distribution by sex, initial motor symptom, location of initial motor symptom, and frequency of asymmetric motor symptoms. RESULTS: Despite different etiologic backgrounds, both familial and sporadic PD exhibited several interesting commonalities, including a higher incidence in men, tremor as the initial motor symptom (predominantly involving the upper extremities), and asymmetric parkinsonism during disease course. CONCLUSIONS: The increased incidence of parkinsonism in men with familial PD suggests that the sex disparity is more likely the result of a protective effect against development of PD in women than of an increased risk in men that is associated with environmental factors. Phenotypic similarity among familial and sporadic PD indicates that a similar topographic distribution of the nigrostriatal lesion exists in patients with either form of PD regardless of apparent genetic influence.

Effect of MAPT and APOE on prognosis of progressive supranuclear palsy.

To assess genetic influence on the clinical presentation of progressive supranuclear palsy (PSP), the genetic effect on disease course was examined for variants in the tau gene (MAPT) and the gene for apolipoprotein E (APOE) in 58 cases of pathologically confirmed PSP. Clinical indicators of disease course included age at symptomatic onset (AAO), age at death (AAD), and disease duration (DD) and the genetic effects examined included MAPT haplotypes and APOE genotypes. From linear regression analysis, the MAPT H1/H1 genotype was associated with significantly earlier AAO (P=0.038). The MAPT genotype did not significantly influence DD or AAD. The APOE epsilon4 allele did not significantly influence AAO, AAD, or DD. Male sex was a predictor for earlier AAO (P=0.015). The interaction between MAPT and APOE was not significant for AAD and DD, but a significant negative coefficient was found for AAO suggesting their combination does not have an additive effect. These results support the assertion that the H1/H1 genotype may contribute to the earlier occurrence of clinical symptoms.