Emiko Ohta

MRI Findings in Neuroferritinopathy

Neuroferritinopathy is a neurodegenerative disease which demonstrates brain iron accumulation caused by the mutations in the ferritin light chain gene. On brain MRI in neuroferritinopathy, iron deposits are observed as low-intensity areas on T2WI and as signal loss on T2∗WI. On T2WI, hyperintense abnormalities reflecting tissue edema and gliosis are also seen. Another characteristic finding is the presence of symmetrical cystic changes in the basal ganglia, which are seen in the advanced stages of this disorder. Atrophy is sometimes noted in the cerebellar and cerebral cortices. The variety in the MRI findings is specific to neuroferritinopathy. Based on observations of an excessive iron content in patients with chronic neurologic disorders, such as Parkinson disease and Alzheimer disease, the presence of excess iron is therefore recognized as a major risk factor for neurodegenerative diseases. The future development of multimodal and advanced MRI techniques is thus expected to play an important role in accurately measuring the brain iron content and thereby further elucidating the neurodegenerative process.

Sympathetic sudomotor and vasoconstrictive neural function in patients with Parkinson's disease

To evaluate sympathetic sudomotor and vasoconstrictive neural function in Parkinsons disease (PD), we simultaneously recorded sympathetic skin response (SSR) and skin blood flow (SVR; skin vasomotor reflex), as well as skin sympathetic nerve activity (SSNA) measured in peroneal nerves by microneurography, comparing 12 patients with idiopathic PD with 16 healthy controls. Resting SSNA frequency (8.8+/-4.3 bursts/min) was significantly lower in PD patients than in controls (p<0.01). Frequency increases in response to performing mental arithmetic were slightly smaller in PD patients than in controls. PD patients exhibited normal SSNA reflex latencies compared with controls. Although no significant relationship was found between resting SSNA frequency and disease duration or degree of disability, a significantly negative correlation between increases in SSNA with mental arithmetic and PD duration was observed. Occurrence of SSR and SVR following SSNA bursts induced by electrical stimuli was reduced in PD (p<0.05). In patients with PD, sympathetic sudomotor and vasoconstrictive neural function was decreased at rest, but SSNA reflex latencies in the legs were nearly normal. Since responses of peripheral target organs may be impaired, both central and peripheral factors may contribute to autonomic symptoms in PD.

Sympathetic sudomotor neural function in amyotrophic lateral sclerosis

Abstract In patients with amyotrophic lateral sclerosis (ALS), sudomotor and vasomotor function have been considered to be impaired based on sympathetic skin response (SSR) or cutaneous blood flow measurements. We evaluated sympathetic sudomotor and vasoconstrictive neural function in ALS. We simultaneously recorded SSR, skin blood flow, and skin sympathetic nerve activity (SSNA) by microneurography in 20 patients with sporadic ALS and 20 healthy controls. Resting frequency of SSNA was significantly higher in ALS patients than in controls (p <0.05), but the increase of SSNA associated with mental arithmetic was smaller in ALS patients than controls (p <0.05). ALS patients also exhibited slight prolongation of SSNA reflex latencies compared with controls (p <0.05). In conclusion, sympathetic hyperactivity was observed in relation to sudomotor and vasoconstrictive skin responses. Since SSNA reflex latencies reflect central sympathetic function, the central autonomic pathways may be slightly impaired in patients with ALS.

Analysis of the relationship between muscle sympathetic nerve activity and cardiac 123I-metaiodobenzylguanidine uptake in patients with Parkinson's disease.

To analyze the correlation between muscle sympathetic nerve activity (MSNA) and cardiac 123I‐metaiodobenzylguanidine (MIBG) uptake in patients with Parkinsons disease (PD), we measured both parameters in 14 PD patients who were 51 to 82 years of age (mean, 63.1 ± 8.7 years). The duration of PD was 2 to 26 years, and the disability level (modified Hoehn and Yahr stage) ranged from 2.0 to 4.0 (mean, 3.2 ± 0.5). MSNA was recorded from the peroneal nerve fascicles using microneurographic methods, and then cardiac MIBG scintigraphy was performed within 1 month. We analyzed the correlation between the standardized MSNA, expressed as a percentage of the predicted value based on control subject data, and the heart‐to‐mediastinum ratio (H/M) or washout ratio (WR) from early and delayed MIBG images. The relationships between disease duration or disability and MSNA, the H/M ratio, or the WR were also analyzed. No significant correlations were found between MSNA and H/M ratio or WR. Although MSNA was inversely correlated with disease duration and with disability level, neither the H/M ratio nor the WR showed a significant correlation with disease duration or disability level. Because MSNA and MIBG abnormalities were not related, functional changes in addition to organic changes in cardiac sympathetic nerve endings may result in abnormal uptake of MIBG in Parkinsons disease.

Cerebral hypermetabolism demonstrated by FDG PET in familial Creutzfeldt-Jakob disease.

Right cerebral and contralateral cerebellar hypermetabolism were observed on FDG PET in a 68-year-old woman with familial Creutzfeldt-Jakob disease (CJD) at an early stage before seizures occurred. The disease progressed with frequent seizures, myoclonus, and a startle reaction. In all past reports, FDG PET studies demonstrated hypometabolism in the cerebrum, cerebellum, and thalamus in patients with CJD. Focal hypermetabolism corresponding with epileptic foci is a common finding in ictal epilepsy patients, and hypometabolism is common in patients with myoclonus or the startle reaction. This finding may reflect a prodromal pathophysiology of epilepsy. Attention should be paid to the diagnosis of CJD while using FDG PET.

A concise overview of recent breakthroughs in imaging of ALS.

Numerous attempts have been made to visualize the motor cortex and pyramidal tract lesions in patients with ALS using magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET). This paper briefly reviews the applicability of these imaging modalities in ALS. (ALS 2000; 1(suppl 2): S3-S6)

Autopsy-proven creutzfeldt-jakob disease with a codon 180 mutation showing dissociation between diffusion-weighted magnetic resonance imaging and single-photon emission computed tomography findings : Is this a suggestive finding in long survival?

Case Report A 79-year-old, previously healthy woman was admitted to our hospital in June 2000 because of progressive dementia and body bradykinesia since December 1999. She was markedly disoriented and showed an abnormal startle reaction, bilateral extrapyramidal signs and myoclonic movements of all limbs. Her family history was noncontributory despite careful inquiry. The results of hematological examinations and blood chemistry tests were unremarkable. A lumbar puncture yielded normal cerebrospinal fluid except for slightly elevated neuron-specific enolase (23.1 ng/ml; normal ! 16 ng/ml) and positive protein 14-3-3. Genetic analysis of PrP revealed a codon 180 point mutation (Val ] Ile) and also a codon 129 polymorphism (Met ] Val). EEG showed a diffuse 7-Hz basic pattern without epileptic or periodic synchronous discharges. T 1 -weighted (TR 900/TE 30 msec) magnetic resonance imaging (1.5-T MRI; Signa, GE Medical Dear Sir, Creutzfeldt-Jakob disease (CJD) is a rare transmissible disease that causes rapidly progressive dementia, myoclonic movements, and both pyramidal and extrapyramidal symptoms [1] . Radiologically, diffusion-weighted magnetic resonance imaging (DWI) is very useful in detecting cortical and basal ganglia abnormalities [2] . In most cases occurrence is sporadic, but a small proportion of cases are familial. Among various associated mutations of the prion protein (PrP) gene identified by genetic analyses, a point mutation at codon 180 has been confirmed in only 7 patients, who characteristically showed a relatively long survival, old-age onset, absence of periodic synchronous discharges on electroencephalography (EEG) and lack of affected family members [3–8] . We report another CJD case with the same mutation of PrP, where neuroradiologic findings showed an unexpected and possibly informative dissociation. Received: October 3, 2005 Accepted: April 12, 2006 Published online: August 17, 2006

Rhythmic pupillary oscillation in Creutzfeldt‐Jakob disease associated with the Glu/Lys mutation of prion protein codon 200

We report two Creutzfeldt‐Jakob disease (CJD) patients with rhythmic pupillary and palpebral oscillation who had a mutation of prion protein codon 200 that resulted in the substitution of lysine for glutamate (Glu/Lys). Alternating dilation and constriction of the pupils combined with elevation and descent of the eyelids occurred in correspondence with periodic sharp wave complexes (PSWCs) on the electroencephalogram and with myoclonus of the head, face, and extremities. The onset of pupillary dilation and palpebral elevation coincided with the PSWCs. Initiation of these rhythmic pupillary and palpebral movements may depend on sympathetic activity, but the site of the generator is unclear. Such rhythmic pupillary and palpebral oscillation may be a feature of rapidly progressive CJD with predominant right hemispheric involvement.

P35.7 Skin vasomotor and sudomotor neural function in patients with amyotrophic lateral sclerosis

miological study revealed a significant association between ACE genotypes and QTc. None of these studies examined the association of ACE gene with QTc and HRV simultaneously. We report our preliminary data on the relationship between ACE polymorphisms, QTc, and HRV in a multiethnic population in rural Hawaii in collaboration with the Autonomic Disorders Center (ADC) at the Mayo Clinic. Methods: Autonomic function tests were performed on subjects according to the protocol developed by the ADC neurologist. Continuous EKG data were obtained during pace deep breathing (HRDB). Each autonomic study was evaluated by the study neurologist at the ADC. All subjects underwent an oral glucose tolerance test to exclude patients with diabetes. Results: Preliminary results revealed a significant statistical interaction between the angiotensin-converting enzyme (ACE) gene polymorphism, prolonged QTc, and decreased HRDB. The insertion allele was associated with significantly longer QTc intervals in individuals with decreased HRDB, but not in individuals with normal HRDB. Conclusions: The results demonstrate QTc duration is apparently moderated by HRV, either indicating QTc interval duration may be influenced by the autonomic modulation of HRV, or alternatively, that HRV may be a marker of decreased cardiac responses to autonomic modulation due to subclinical heart disease.