Nobuyuki Eura

Risk of Falling in Parkinson’s Disease at the Hoehn-Yahr Stage III

Background: It is difficult to predict the risk of falling, especially in patients with good motor ability, and the mechanisms underlying the relation between gait patterns and falling in Parkinson’s disease (PD) remain unclear. We investigated factors related to falling, including walking speed and time, in patients with Hoehn-Yahr stage III PD. Methods: We performed clinical assessments and evaluated balance in 30 patients with PD. Information on falling was obtained from questionnaires and personal interviews. Gait patterns were analyzed with the use of an originally designed, suddenly narrowed path. Results: Gait velocity was slower in fallers than in non-fallers (p = 0.047). Unified Parkinson’s Disease Rating Scale part II (UPDRS part II) score, fear of falling, and gait velocity were significantly related to falling on analysis with a single logistic model. When a multiple logistic model was used, the UPDRS part II score was significantly related to falling (OR: 1.48, p = 0.037, 95% CI: 1.02–2.16). Conclusions: Patients with Hoehn-Yahr stage III PD showed slow gait velocity attributed to fear of falling before arrival at a narrowed entrance or while walking on a narrowed path. The UPDRS part II score is significantly related to the risk of future falls.

Early onset of cardiomyopathy and intellectual disability in a girl with Danon disease associated with a de novo novel mutation of the LAMP2 gene

Danon disease, primary lysosome‐associated membrane protein‐2 (LAMP‐2) deficiency, is characterized clinically by cardiomyopathy, myopathy and intellectual disability in boys. Because Danon disease is inherited in an X‐linked dominant fashion, males are more severely affected than females, who usually have only cardiomyopathy without myopathy or intellectual disability; moreover, the onset of symptoms in females is usually in adulthood. We describe a girl with Danon disease who presented with hypertrophic cardiomyopathy and Wolff‐Parkinson‐White (WPW) syndrome at 12 years of age. Subsequently, she showed signs of mild learning disability and intellectual disability on psychological examinations. She had a de novo novel mutation in the LAMP‐2 gene and harbored an identical c.749C > A (p.Ser250X) variant, resulting in a stop codon in exon 6. She showed decreased, but not completely absent LAMP‐2 expression on immunohistochemical and Western blot analyses of a skeletal muscle biopsy specimen, which has been suggested to be caused by a 50% reduction in LAMP‐2 expression (LAMP‐2 haploinsufficiency) in female patients with Danon disease caused by a heterozygous null mutation. To our knowledge, our patient is one of the youngest female patients to have been given a diagnosis of Danon disease. In addition, this is the first documented case in a girl that was clearly associated with intellectual disability, which is very rare in females with Danon disease. Our findings suggest that studies of female patients with Danon disease can extend our understanding of the clinical features of this rare disease.

Painful abdominal contractions in patients with Parkinson disease

We hypothesized that the unusual and painful abdominal contractions in two of our patients with Parkinson disease (PD) were linked to abdominal muscle hypertrophy. The abdominal pain was aggravated by sitting, standing, or walking, and was characterized by a powerful pulling sensation associated with palpable contractions of the rectus abdominis. When the pain decreased, the camptocormia abated. The thickness of the rectus abdominis and the relative muscle thickness ratio were greater in the two patients with abdominal contractions than in the control patients with PD without abdominal contractions. Palpable painful abdominal contractions could be associated with the presence of hypertrophy of the rectus abdominis visible on CT scan. The abdominal muscle contractions probably contribute to the development a stooped posture.

Comparison of brain 3.0-T with 1.5-T MRI in patients with multiple sclerosis: A 6-month follow-up study

OBJECTIVES The 2010 revisions to the McDonald criteria for the diagnosis of multiple sclerosis (MS) were recently published. One objective of the revision was to simplify the MRI criteria. The MRI criteria do not specify magnetic field strength. We studied whether there was any difference in diagnosis between brain 3.0-T and 1.5-T MRI according to the 2010 revisions of the McDonald criteria. PATIENTS AND METHODS We prospectively studied brain 3.0-T and 1.5-T MRI in 22 patients with MS. 1.5-T MRI was performed 24h after 3.0-T MRI, and the scanning protocol included contiguous axial sections of T2-weighted images (T2WI), T1WI, and enhanced T1WI. These two different MRI and neurological assessments were scheduled to be repeated 3 and 6 months after study entry. RESULTS The regions where MS lesions were better visualized on 3.0-T MRI tended to be in deep white matter on T2WI. Dissemination of lesions in space and time was similar for 3.0-T and 1.5-T MRI. CONCLUSION Our study found no difference between brain 3.0-T and 1.5-T MRI. There was no apparent impact of brain 3.0-T MRI on the diagnosis of MS according to the 2010 version of the MRI criteria.

Dropped head with positive intravenous edrophonium, progressing to myasthenia gravis

‘Dropped head syndrome’ (DHS) may be associated with a variety of neurological diseases. The absence of neurological clues to the underlying cause of DHS can make management particularly challenging. We review six patients who presented with only DHS, responded to intravenous edrophonium and turned out to have myasthenia gravis (MG) including similar patients who were previously documented. Six patients presented with neck weakness and three had bulbar symptoms. Acetylcholine receptor (AchR) was positive in four patients. One patient had thymoma. The interval from the onset of DH to the presentation of typical MG features was shorter in patients who tested positive for anti-Ach antibody (1–2 months) than in patients who tested negative for anti-AchR antibody (13 months, 4 years). Our results suggest that patients with DHS responding to intravenous edrophonium might turn out to have MG and such patients might respond to a combination of anticholinesterase agents and steroids.

Paradoxical Gait at a Narrowed Entrance in a Patient with Hoehn-Yahr Stage III Parkinson’s Disease

Recently, we studied fallers and non-fallers with Hoehn-Yahr stage III Parkinson’s disease (PD) using a path that suddenly narrowed, which we originally designed and produced. A risk of future falls was suggested to be related to slow gait with freezing (SGF) elicited by a fear of falling before arrival at a narrowed entrance or while walking on a narrow path, as well as to the Unified Parkinson’s Disease Rating Scale part II score, associated with SGF. In the same study, we had faller patients walk on a path that narrowed in a straight-line fashion to determine whether SGF could be improved. In one patient, who showed a unique paradoxical gait, SGF resolved. We describe this patient in the hope that our experience will provide potential clues to effective ways to prevent future falls in patients with Hoehn-Yahr stage III PD. To prevent gait instability elicited by fear of falling in patients with Hoehn-Yahr stage III PD, it might be useful to remove narrowed entrances.

A Patient With Encephalomyeloradiculoneuropathy Exhibiting a Relapsing–Remitting Clinical Course: Correlation of Serum and Cerebrospinal Fluid Anti-Neutral Glycosphingolipids Antibodies With Clinical Relapse

Several patients who had a progressive clinical course involving both the central and peripheral nervous systems have been reported, but the diagnostic marker has been remained uncertain. More recently, such patients were reported to have namely “encephalomyeloradiculoneuropathy (EMRN)” associated with anti-neutral glycosphingolipid (GSL) antibodies. These antibodies were reported to disappear from the serum in the recovery phase, but whether this finding applies to the cerebrospinal fluid (CSF) remains uncertain. We describe a 67-year-old man with EMRN in whom we measured anti-neutral GSL antibodies in serial serum and CSF samples. During the disease course, the optical densities of the positive band against the background intensity ratio (–<0.3; ±≥0.3 to <0.6; +≥0.6 to <1.0; 2+≥1.0 to <2.0; 3 +≥2.0) for serum and CSF anti-lactosylceramide (LacCer) antibodies were found to be as follows: 2+ and 1+ at the first admission, ± and − when the consciousness level improved after immunotherapy, − and 1+ at clinical relapse, and ± and − when the consciousness level improved after immunotherapy. This is the first time to document that clinical relapse occurred in EMRN, and at this time the negative anti-LacCer antibodies in CSF after the first course of immunotherapy turned positive, but this was not seen in serum samples.

Step Numbers and Hoehn-Yahr Stage after Six Years

Background: Freezing of gait (FOG) has been linked to increased numbers of steps taken while walking. We tested the hypothesis that an increased number of steps associated with FOG might predict the exacerbation of the severity of Parkinson’s disease (PD). Methods: We prospectively studied 26 patients. Clinical assessments were performed and balance was evaluated in 30 patients with Hoehn-Yahr stage III PD 6 years previously. Gait parameters were analyzed with the use of an originally designed, suddenly narrowed path. PD-related independent variables, balance investigation-related variables, and gait-independent-related variables were analyzed by multiple logistic regression analysis. Results: The Hoehn-Yahr stage increased in 14 patients and was unchanged in 12 patients. The 36-item Short-Form Health Survey score (OR 1.079, p = 0.041, 95% CI 1.003–1.161) and the number of steps on the suddenly narrow path (OR 1.605, p = 0.047, 95% CI 1.006–2.56) were related to an increase in the Hoehn-Yahr stage. The number of steps was significantly higher on the suddenly narrowed path (11.3 ± 3.6) than on a straightly narrowed path (10.1 ± 3.2) at the time of final follow-up in the 26 patients (p < 0.001). Conclusions: An increased number of steps associated with FOG, which was elicited by the suddenly narrowed path, might be one predictor of an upgrade of stage in patients with Hoehn-Yahr stage III PD.

Characteristics of Risk-Factor Profiles Associated with Stroke in Patients with Myotonic Dystrophy Type 1

Objective: Myotonic dystrophy type 1 (DM1) is a rare autosomal dominant disorder with highly variable phenotypic expression. Some patients have diabetes mellitus, dyslipidemia, and/or arrhythmias, which are risk factors for stroke. However, the mechanism of stroke is poorly understood in patients with DM1. We studied the characteristics of risk-factor profiles for stroke associated with DM1. Patients and methods: We studied 77 patients with DM1 (45 men and 32 women) on the basis of the patients’ clinical histories and laboratory and genetic examination results. Results: The analysis showed that 26 patients (34%) had dyslipidemia, and 16 (21%) had diabetes. Arrhythmias were diagnosed in 46 patients (61%), including 11 (14%) with atrial fibrillation and 9 (12%) with conduction defects. Echocardiographic abnormalities were found in 28 patients (37%). Eight patients (11%) met the criteria for metabolic syndrome. We identified 2 patients (2.6%) with ischemic stroke caused by cardiogenic embolism among 77 patients with DM1. One had paroxysmal atrial fibrillation and sick sinus syndrome, and the other had cardiac dysfunction with an ejection-fraction of 35% and dyslipidemia. Both patients had highly expanded numbers of CTG repeats (1000 and 1500). Conclusion: To our knowledge, this is the first study to report a comprehensive analysis of risk-factor profiles for stroke in patients with DM1. Stroke is a relatively rare, but severe complication of DM1. Our results indicate that it is important to manage risk factors for stroke, especially cardiac involvement and arrhythmias.

Characteristic dysphagia as a manifestation of dermatomyositis on oropharyngeal muscle imaging.

A 40-year-old woman presented with progressive skin rash, muscle weakness of all 4 limbs, dysphagia, and nasal voice over 3 weeks. Erythematous rashes were present on the arms, trunk, and face. The serum creatine kinase (CK) levelwas elevated (1794 IU/L). Electromyography showedmyopathic changes. A biopsyof thebicepsmuscle revealedmyopathic changeswithcharacteristic perifascicular muscle fiber atrophy. Major histocompatibility