Maiko Murakami

Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease

BACKGROUND In our previous study, higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and the vitamin D receptor (VDR) FokI CC genotype were associated with milder Parkinson disease (PD). OBJECTIVE We evaluated whether vitamin D3 supplementation inhibits the progression of PD on the basis of patient VDR subgroups. DESIGN Patients with PD (n = 114) were randomly assigned to receive vitamin D3 supplements (n = 56; 1200 IU/d) or a placebo (n = 58) for 12 mo in a double-blind setting. Outcomes were clinical changes from baseline and the percentage of patients who showed no worsening of the modified Hoehn and Yahr (HY) stage and Unified Parkinsons Disease Rating Scale (UPDRS). RESULTS Compared with the placebo, vitamin D3 significantly prevented the deterioration of the HY stage in patients [difference between groups: P = 0.005; mean ± SD change within vitamin D3 group: +0.02 ± 0.62 (P = 0.79); change within placebo group: +0.33 ± 0.70 (P = 0.0006)]. Interaction analyses showed that VDR FokI genotypes modified the effect of vitamin D3 on changes in the HY stage (P-interaction = 0.045), UPDRS total (P-interaction = 0.039), and UPDRS part II (P-interaction = 0.021). Compared with the placebo, vitamin D3 significantly prevented deterioration of the HY stage in patients with FokI TT [difference between groups: P = 0.009; change within vitamin D3 group: -0.38 ± 0.48 (P = 0.91); change within placebo group, +0.63 ± 0.77 (P = 0.009)] and FokI CT [difference between groups: P = 0.020; change within vitamin D3 group: ±0.00 ± 0.60 (P = 0.78); change within placebo group: +0.37 ± 0.74 (P = 0.014)] but not FokI CC. Similar trends were observed in UPDRS total and part II. CONCLUSION Vitamin D3 supplementation may stabilize PD for a short period in patients with FokI TT or CT genotypes without triggering hypercalcemia, although this effect may be nonspecific for PD. This trial was registered at UMIN Clinical Trials Registry as UMIN000001841.

25-hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson's disease.

We aimed to examine associations among serum 25‐hydroxyvitamin D levels, 1,25‐dihyroxyvitamin D levels, vitamin D receptor polymorphisms, vitamin D binding protein gene polymorphisms, and the severity of Parkinsons disease. In 137 patients, the severity of Parkinsons disease was evaluated using Hoehn & Yahr stage and Unified Parkinsons Disease Rating Stage by neurologists and compared with 25‐hydroxyvitamin D, 1,25‐hydroxyvitamin D, vitamin D receptor polymorphisms, ie, FokI (rs10735810), BsmI (rs1544410), Cdx2 (rs11568820), ApaI (rs7976091), and TaqI (rs731236), and vitamin D binding protein gene polymorphisms GC1 (rs7041)/GC2 (rs4588) in a cross‐sectional study. Mean ± standard deviation levels of 25‐hydroxyvitamin D were 21.1 ± 9.0 ng/mL. Levels were deficient (<20 ng/mL) in 49% of patients. In contrast, 1,25‐hydroxyvitamin D levels were considered normal in all patients. Higher circulating 25‐hydroxyvitamin D levels were significantly associated with milder Parkinsons disease evaluated by Hoehn & Yahr stage (P = .002) and total Unified Parkinsons Disease Rating Stage (P = .004) even after multivariate adjustment for 8 covariates, including disease duration. However, significant associations were not observed in 1,25‐hydroxyvitamin D levels. Under multivariate analysis with 25‐hydroxyvitamin D as well as other 8 covariates including disease duration, carriers of vitamin D receptor FokICC genotype had a milder form of Parkinsons disease: odds ratio, 0.32; 95% confidence interval, 0.16 to 0.66, P = 0.002. These results suggest that higher 25‐hydroxyvitamin D levels and the vitamin D receptor FokICC genotype may be independently associated with milder forms of Parkinsons disease. However, significant associations were not observed in 1,25‐hydroxyvitamin D levels.

Visual hallucinations and altered visual information processing in Parkinson disease and dementia with Lewy bodies

Visual hallucinations (VHs) are common in dementia with Lewy bodies (DLB) and Parkinsons disease with dementia (PDD), while auditory hallucinations are rare. To neurophysiologically investigate the pathophysiology of VHs in these disorders, we studied event‐related potentials (ERPs) of DLB, PDD, and Alzheimers disease (AD) patients. We compared visual and auditory ERP latencies among PDD patients with and without VHs (PDD‐H: 11, PDD‐N: 6), DLB patients (24), and AD patients (21). To elicit visual and auditory ERPs, a facial discrimination paradigm and a conventional auditory odd‐ball paradigm, respectively, were used. The mean visual P3 latencies in the PDD‐H and DLB groups were significantly longer than that in the AD group, while the mean auditory P3 latencies in all four patient groups were comparable. The mean visual P2 latencies in the PDD‐N, PDD‐H, and DLB groups were significantly longer than that in the control group. Our findings suggest that visual cognitive functions are selectively impaired in hallucinatory patients with DLB and PDD. VHs may be associated in part with predominant visual cognitive impairments attributable to PDD and DLB pathologies. Our findings also suggest that the impairments occur at the early stage of facial information processing.

The odor stick identification test for Japanese differentiates Parkinson's disease from multiple system atrophy and progressive supra nuclear palsy

BackgroundProgressive supranuclear palsy (PSP) and parkinsonian variant of multiple system atrophy (MSA-P) are clinically difficult to differentiate from idiopathic Parkinsons disease (PD), particularly in the early stages of the disease. Previous reports indicated that the olfactory function is relatively intact or slightly reduced in patients with PSP and MSA-P, suggesting that the odor stick identification test for Japanese (OSIT-J), which is a short and simple noninvasive test that is potentially useful clinically for detecting early-stage PD in Japan, may be useful in the differential diagnosis of early-stage PD from MSA-P and PSP. There is no information on the sensitivity and specificity of OSIT-J in the diagnosis of parkinsonian syndromes such as PSP and MSA-P.MethodsWe assessed the olfactory function using the OSIT-J test in 94 Japanese patients with idiopathic PD, 15 with MSA-P, 7 with PSP, and 29 age-matched control subjects.ResultsThe mean ± SD score of OSIT-J in patients with PD (4.4 ± 2.9) was significantly lower than in patients with MSA-P (8.7 ± 2.2, P < 0.0001), PSP (7.6 ± 2.2, P < 0.0057), and control subjects (10.5 ± 1.3, P < 0.0001). The area under the curve (AUC) of receiver operating characteristic (ROC) to discriminate PD from normal control using OSIT-J scores was 0.97 (95% confidence interval, 0.95-1.00), from MSA-P 0.87 (0.80-0.95), and from PSP 0.81 (0.66-0.96).ConclusionThe OSIT-J is a potentially useful clinical test not only for detection of olfactory deficit in PD but also for differentiating PD from MSA-P and PSP.

A case of segmental zoster paresis with enhanced anterior and posterior spinal roots on MRI

Herpes zoster is an infectious disease caused by reactivation of the varicella zoster virus (VZV) in the dorsal root ganglia [2]. Neurological complications other than sensory abnormalities such as encephalitis, myelitis, and various lower motor neuron diseases such as polyradiculoneuritis as segmental radiculitis have been reported [7]. Segmental zoster paresis is characterized by focal motor weakness that appears in the same segment where the skin eruptions, neuralgia, and sensory symptoms occur, and is a relatively common complication [1, 3, 6, 7]. We report a patient in whom the radiological findings were consistent with aberration of anterior and posterior spinal roots with zoster paresis. A 73-year-old man developed right shoulder pain and herpes zoster eruptions over the C5 dermatome. Two days later, he found it impossible to lift up the right arm. He was admitted to our hospital with 2-week history of shoulder pain and progressive muscle weakness around the right shoulder. Physical examination on admission showed weakness of the upper extremity in the distribution of the right C5 myotome and sensory disturbance in the right C5 dermatome, but no clinical symptoms of myelitis. Laboratory findings showed VZV-IgM level of 4.30 mg/dl (normal \0.8 mg/dl). Examination of cerebrospinal fluid (CSF) showed 102.8 cells/mm, protein content of 66.8 mg/dl, and elevated varicella zoster virus IgG titer (antibody index [4). Polymerase chain reaction (PCR) of CSF fluid was positive for VZV DNA, but no search for the number of copies was performed. Needle electromyography showed neurogenic changes in the right deltoid and biceps brachii muscles. T1-weighted magnetic resonance imaging (MRI) showed contrast enhancement with gadolinium in the right anterior and posterior C5 spinal roots below the 4th cervical vertebra (Fig. 1b), but no abnormal contrast enhancement of the roots of the 4th and 6th spinal nerves (Fig. 1a, c). Furthermore, T2-weighted MRI showed no abnormal intensity in the cervical spinal cord. The patient was treated with intravenous 1,500 mg acyclovir for 7 days together with rehabilitation. Examination about 1 month later showed improvement of muscle weakness and disappearance of the shoulder pain. The MRI findings suggested VZV reactivation in the dorsal root ganglia, which was localized to the anterior and posterior C5 spinal roots, based on the motor and sensory symptoms of C5 dermatome and myotome. The spread of VZV from the posterior spinal root, or anterior and posterior horn, to the anterior spinal root could have resulted from inflammation. CSF analysis indicated pleocytosis and serologically confirmed VZV. Previous studies reported abnormalities of CSF in 61% of patients with VZV and subclinical extension of viral inflammation into the central nervous system [4]. The clinical symptoms and MRI findings in our patient were not confirmative for myelitis. We postulate the spread of VZV either directly or through the CSF, rather than myelitis, from the posterior spinal root to the anterior spinal root in our patient. The cause of the nerve root enhancement was considered to be due to either viral activation itself or associated inflammation. Previous MRI findings in zoster paresis showed myelitis [3], posterior root with anterior horn [9] and posterior horn [8], suggesting myelitis and anterior root [5], suggesting disruption of the blood–brain barrier. Post mortem M. Yoshioka (&) Y. Kurita M. Hashimoto M. Murakami M. Suzuki Department of Neurology, Aoto Hospital, The Jikei University School of Medicine, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan e-mail: m.yoshioka@jikei.ac.jp