[Clinical and neuropsychological features and changes to regional cerebral blood flow in |patients with Parkinson's disease dementia].

This study aimed to clarify associations of clinical and neuropsychological features and change in regional cerebral blood flow (rCBF) on 123I-IMP-SPECT in patients with Parkinson's disease (PD) who developed dementia. Sixty-one PD patients (mean age, 65.9 ± 8.6 years; mean disease duration, 11.0 ± 11.0 years) were recruited and followed-up for two years. Clinical and neuropsychological characteristics, and rCBF from SPECT were compared between PD patients who developed dementia (PDD+) and those who remained undemented (PDD-). Thirty-eight PD patients (62.3%) were diagnosed with PD-MCI at baseline. During follow-up, 22 PD patients (36%) developed dementia (PDD+). Univariate logistic regression models showed that Hoehn and Yahr scale 4 (odds ratio [OR] 5.85; 95% confidence interval [CI] 1.35-30.75]), visual hallucination (OR 5.95; 95%CI 1.67-25.4]), and PD-MCI (OR 6.47; 95%CI 1.57-39.63]) represented a significant risk factor for PDD+. Among neuropsychological parameters, WAIS (Wechsler Adult Intelligence Scale)-III block design (OR 6.55; 95%CI 1.66-29.84), letter number sequencing (OR 7.01; 95%CI 1.65-36.64), digit-symbol coding (OR 3.90; 95%CI 1.13-14.2), Wechsler Memory Scale, revised (WMS-R) visual paired associates II (delayed recall) (OR 4.68; 95%CI 1.36-17.36), Logical memory I (immediate recall) (OR 8.30; 95%CI 1.37-90.89), Logical memory II (delayed recall) (OR 6.61; 95%CI 1.35-44.33), Visual reproduction I (immediate recall) (OR 7.67; 95%CI 2.11-31.40), and Visual reproduction II (delayed recall) (OR 5.64; 95%CI 1.62-21.47) were significant risk factors. Decreased rCBF assessed using the general linear model (two-sample t-test) by SPM8 was observed in the left precuneus (0, -66, 16), right cuneus (6, -76, 30), and left angular gyrus (-46, -74, 32) in PDD+ compared with PDD- patients. Collectively, we have here shown that clinical and neuropsychological characteristics as well as changes to rCBF in PD patients who converted to PDD+. These features should be carefully monitored to detect the development of dementia in PD patients.

A fatal neuromuscular disease in an adult patient after poliomyelitis in early childhood: consideration of the pathology of post-polio syndrome.

Post-polio syndrome (PPS) characterized by new neuromuscular problems can appear many years after acute poliomyelitis in polio survivors. We report a 77-year-old man with antecedent poliomyelitis who newly developed neuromuscular disease with a clinical course of 27 years, the final 10 years of which were characterized by apparent progression, thus raising doubt as to the clinical diagnosis of amyotrophic lateral sclerosis (ALS) following PPS. Pathologically, plaque-like, old poliomyelitis lesions were found almost exclusively in the lumbosacral cord, showing complete neuronal loss and glial scars in the anterior horns. Although less severe, neuronal loss and gliosis were also evident outside the old lesions, including the intermediate zone. Moreover, symmetrical degeneration of the corticospinal tracts, as evidenced by CD68 immunostaining, was a feature of the white matter of the lower spinal cord. In the motor cortex, loss of Betz cells was also confirmed. Synaptophysin immunostaining of the lumbosacral cord also revealed decreased expression outside the old lesions, excluding the posterior horn. Interestingly, decreased expression of synaptophysin was also evident in the cervical anterior horns, where no old lesions were observed. No Bunina bodies, TDP-43 inclusions, or Golgi fragmentation were found. Neurogenic atrophy was evident in the iliopsoas and scalenus muscles, and inclusion body myositis-like changes were also observed in these muscles and the tongue. Was it possible to have diagnosed this patient as having ALS? We consider that the features in this case may have represented the pathology of long-standing and/or fatal PPS itself, and not ALS.

[Case of hereditary Y69H (p.Y89H) transthyretin variant leptomeningeal amyloidosis presenting with drop attacks and recurrent transient language disorder].

We report a 73-year-old woman who started developing recurrent transient aphasia at the age of 66 years. During the attacks, she was aware she could not understand what was being said and both her spoken and written speech were meaningless. The attacks usually lasted for a few days, following which she could explain what had happened. Anti-epileptics did not improve her symptoms. She also noticed tremor of her right hand and gait disturbance at the age of 71 years. The recurrent transient aphasia was followed by drop attacks. At the time of her admission to our hospital, she showed paraplegia, phonological paraphasia, and difficulty in understanding complex sentences. Her language disturbance resembled a logopenic variant of primary progressive aphasia. However, the symptoms fluctuated for a few days and subsequently improved. Electroencephalography showed no abnormalities. Gadolinium-enhanced brain and spinal MRI showed diffuse leptomeningeal enhancement over the surface of the spinal cord, brain stem, and cerebrum on T1-weighed imaging. Surgical biopsy of a varicose vein in the subarachnoid space at the level of the Th11 spinal cord was performed. Pathological evaluation of the biopsied specimens revealed TTR-immunolabeled amyloid deposits in the subarachnoid vessel walls and on the arachnoid membrane. Gene analysis revealed c.265T>C, p.Y89H (Y69H) TTR mutation, which is known as one of the causative mutations of familial leptomeningeal amyloidosis. Leptomeningeal forms of transthyretin amyloidosis might present transient focal neurological episodes.

[Neuropsychological and regional cerebral blood flow of posterior parietal area features in patients with Parkinson's disease with mild cognitive impairment].

This study aimed to clarify associations between neuropsychological scales and regional cerebral blood flow (rCBF) of on |123I-IMP-SPECT in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). Forty-two participants (mean age, 65.5 ± 8.9 years; mean disease duration, 11.1 ±5.7 years) were evaluated using the Wechsler Adult Intelligence Scale, third edition (WAIS-III), Wechsler Memory Scale, revised (WMS-R), Stroop test, Category word fluency, Auditory verbal learning test, Raven colored progressive matrices, Trail Making Test-B, and Clock drawing test. Participants were classified into PD-MCI and PD non-demented (PD-ND) using ten of these scales or its subtests. The rCBF of the posterior cingulate gyrus, precuneus, and parietal lobes was evaluated by |123I-IMP-SPECT using the easy Z-|score imaging system (eZIS analysis). Extent was the extent index of voxels showing z-score > 2, and Severity was mean z-score in those regions on eZIS analysis. Cingulate island sign score (CIScore) was the ratio of integrated z-scores of the posterior cingulate gyrus to those of the posterior cortex.Twenty-three participants were diagnosed with PD-MCI (55%). The rCBF indices were significantly increased in the PD-MCI group compared to the PD-ND group (Extent: P = 0.047; CIScore: P = 0.006). These indices were significantly correlated with WAIS-III Processing Speed (Extent: P = 0.041, R = -0.317; Severity: P = 0.047, R = -0.309), Stroop effect (Extent: P = 0.003, R = 0.443; Severity: P = 0.004, R = 0.437), WMS-R Visual memory (Extent: P = 0.019, R = -0.361; Severity: P = 0.014, R = -0.375), and Delayed memory score (Extent: P = 0.005, R = -0.423; Severity: P = 0.044, R = -0.312). The rCBF indices showed no correlations with the number of impaired cognitive domains. Collectively, decreased posterior parietal area rCBF and lower scores on selective neuropsychological scales might be helpful to detect a transition period from PD-MCI to PD-D.

Biallelic COX10 Mutations and PMP22 Deletion in a Family With Leigh Syndrome and Hereditary Neuropathy With Liability to Pressure Palsy.

Objectives: Leigh syndrome is a progressive encephalopathy characterized by symmetrical lesions in brain. This study aimed to investigate the clinicopathologic and genetic characteristics of a family with Leigh syndrome and hereditary neuropathy with liability to pressure palsy (HNPP). Methods: Data from a Japanese family's clinical features, MRIs, muscle biopsy, and an autopsy were analyzed. A whole-exome sequence was performed, as well as real-time PCR analysis to determine copy number variations and Western blot analyses. Results: The proband and her 2 siblings developed spastic paraplegia and mental retardation during childhood. The proband and her sister had peripheral neuropathy, whereas their father developed compression neuropathy. Leigh encephalopathy was diagnosed neuropathologically. Brain MRI revealed changes in cerebral white matter as well as multiple lesions in the brainstem and cerebellum. Muscle biopsy revealed type 2 fiber uniformity and decreased staining of cytochrome c oxidase. The COX10 missense mutation was identified through whole-exome sequence. A 1.4-Mb genomic deletion extending from intron 5 of COX10 to PMP22 was detected. Discussion: These findings suggest that in this family, Leigh syndrome is associated with a mitochondrial respiratory chain complex IV deficiency caused by biallelic COX10 mutations coexisting with HNPP caused by heterozygous PMP22 deletion.

Successful twin pregnancy in a patient with parkin-associated autosomal recessive juvenile parkinsonism.

BACKGROUND: Pregnancy in patients with Parkinson disease is a rare occurrence. To the best of our knowledge, the effect of pregnancy as well as treatment in genetically confirmed autosomal recessive juvenile parkinsonism (ARJP) has never been reported. Here, we report the first case of pregnancy in a patient with ARJP associated with a parkin gene mutation, ARJP/PARK2. CASE PRESENTATION: A 27-year-old woman with ARJP/PARK2 was diagnosed as having a spontaneous dichorionic/diamniotic twin pregnancy. Exacerbation of motor disability was noted between ovulation and menstruation before pregnancy as well as during late pregnancy, suggesting that her parkinsonism might have been influenced by fluctuations in the levels of endogenous sex hormones. During the organogenesis period, she was only treated with levodopa/carbidopa, although she continued to receive inpatient hospital care for assistance in the activities of daily living. After the organogenesis period, she was administered sufficient amounts of antiparkinsonian drugs. She delivered healthy male twins, and psychomotor development of both the babies was normal at the age of 2 years. CONCLUSION: Pregnancy may worsen the symptoms of ARJP/PARK2, although appropriate treatments with antiparkinsonian drugs and adequate assistance in the activities of daily living might enable successful pregnancy and birth of healthy children.

Long-term disability and prognosis in dentatorubral-pallidoluysian atrophy: a correlation with CAG repeat length.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder caused by CAG repeat expansion. Previous studies demonstrated that the onset of DRPLA is closely associated with CAG repeat length. However, the natural history of DRPLA has not yet been evaluated. We here retrospectively investigated the factors that determine the disease milestones and prognosis in 183 Japanese patients genetically diagnosed with DRPLA. We determined the age at onset, age at which each of the subsequent clinical manifestations appeared, age at becoming wheelchair-bound, and age at death. Kaplan-Meier analysis revealed that the patients with CAG repeats larger than the median length of 65 repeats developed each of the clinical features of DRPLA at a younger age than those with <65 repeats. The patients became wheelchair-bound at a median age of 33 years (n = 61; range, 3-77 years) and died at a median age of 49 years (n = 23; range, 18-80 years). The ages at becoming wheelchair-bound and at death strongly correlated with the expanded CAG repeat length. Moreover, the patients with >or=65 CAG repeats showed a more severe long-term disability and a poorer prognosis. In contrast, the rate of progression after the onset did not correlate with CAG repeat length. The CAG repeat length may have a considerable effect on not only the disease onset but also the disease milestones and prognosis in DRPLA patients. These effects of CAG repeat length may be relevant in designing future clinical therapeutic trials.

[An apraxia of eyelid closure in association with frontal lobe atrophy in a patient with amyotrophic lateral sclerosis].

A 57 year-old woman with amyotrophic lateral sclerosis (ALS) and an apraxia of eyelid closure was reported. Her first symptom was muscle weakness in the right arm. Since neurological examination showed mainly upper motor neuron sign with neurogenic pattern in the needle electromyograms of the tongue and limb muscles, she was diagnosed as ALS. Two years and 6 months later from onset, she showed an inability to close her eyelids voluntarily or on command with normal reflex closure. MRI of the brain showed atrophy in the frontal lobe and anterior of the temporal lobe, where 123 I-IMP SPECT revealed hypoperfusion. Considering previous reports, there might be an ALS subset who showed atrophy of frontal lobe together with apraxia of eyelid closure.

[Two cases of generalized tetanus presenting with dysphagia as an initial symptom].

We describe two patients with generalized tetanus, a 60-year-old man and a 76-year-old woman, presenting with dysphagia as an initial symptom of the disease. Eighty percent of patients with generalized tetanus manifest dysphagia on admission to a hospital. However, dysphagia is rare as an initial symptom. Both our patients had dysphagia as their initial symptom, followed by neck stiffness and trismus. We made a diagnosis of generalized tetanus based on these neurological findings in the absence of an apparent episode of trauma. After the administration of tetanus immunoglobulin on admission, they recovered without exhibiting generalized convulsion, autonomic storm, or any other serious complications. The vaccination of tetanus toxoid cannot maintain sufficient antibody titers more than ten years. Therefore, elderly people are considered susceptible to tetanus. We suggest that tetanus should be considered in the differential diagnosis of dysphagia particularly in elderly patients. We also suggest that treatment of tetanus should be initiated immediately, because tetanus still has a high mortality rate at present.