[Clinical feature of neuroferritinopathy].

Neuroferritinopathy is an autosomal dominant, adult-onset disorder characterized by the deposition of iron and ferritin in the brain and a decreased level of serum ferritin. The disease is caused by mutations of the gene encoding ferritin light chain polypeptide. Seven pathogenic mutations have so far been reported, and two of the mutations were found in Japanese families. The mutations are predicted to affect tertiary structure and stability of the ferritin light chain polypeptide and may cause inappropriate iron release from feritin polymers. The excess iron may cause oxidative stress and lead to cell and tissue damage. The typical clinical features are dystonia and involuntary movement. Some patients may present cerebellar ataxia and cognitive decline. The clinical features appear to be restricted to the nervous system. The variety of MRI findings including T(2) hypointense lesions reflecting iron deposits, cystic degeneration of the basal ganglia, and cortical atrophy are characteristic of neuroferritinopathy. Iron depletion therapy by iron chelation in symptomatic patients has not been shown to be beneficial. Recent study shows the iron deposition in neuroferritinopathy begins in early childhood before symptomatic presentation. This finding suggests the importance of early intervention of therapy.

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.

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.

Sympathetic sudomotor neural function in amyotrophic lateral sclerosis.

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.

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.

[Clinical features of neuroferritinopathy].

Neuroferritinopathy is an autosomal dominant basal ganglia disease with iron accumulation caused by a mutation of the gene encoding ferritin light polypeptide (FTL). Six pathogenic mutations in the FTL gene have so far been reported. One such mutation was found in a Japanese family, thus suggesting that a new mutation in the FTL gene can therefore occur anywhere in the world. The typical clinical features of neuroferritinopathy are dystonia (especially orofacial dystonia related to speech and leading to dysarthrophonia) and involuntary movement, but such features vary greatly among the affected individuals. The findings of excess iron storage and cystic changes involving the globus pallidus and the putamen on brain MRI. and low serum ferritin levels are characteristic in neuroferritinopathy. Brain histochemistry shows abnormal aggregates of ferritin and iron throughout the central nervous system. Iron atoms are stored in the central cavity of the ferritin polymer and the E-helices of ferritin play an important role in maintaining the central cavity. A mutation in exon 4 of the FTL gene is known to alter the structure of E-helices, thereby leading to the release of free iron and excessive oxidative stress. Iron depletion therapy by iron chelation in symptomatic patients has not been shown to be beneficial, however before the nset of clinical symptoms, such a treatment strategy may still have some benefit. Neuroferritinopathy should therefore be considered in all patients presenting with basal ganglia disorders of unknown origin. These characteristic MRI findings may help to differentiate neuroferritinopathy from other diseases showing similar clinical features.

(1-Pyridinio)perfluorophenacylide: a new stable pyridinium ylide in the enol form.

The title compound, C(13)H(6)F(5)NO, exists in the enol form and adopts the E configuration about the enol double bond. It is the first example of an enol-type pyridinium ylide. The enol structure was unambiguously determined on the basis of the significantly longer C-O bond and shorter C-C bond. Intramolecular C-H...O and C-H...F hydrogen bonds are responsible for promotion of the enol form and for the stability of this compound.

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

To evaluate sympathetic sudomotor and vasoconstrictive neural function in Parkinson's 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.

Influence of equine conformation on rider oscillation and evaluation of horses for therapeutic riding.

To obtain basic knowledge about selecting horses for therapeutic riding, the influence of equine conformation on rider oscillation and relationships between these factors and the evaluation on horses as the therapeutic riding were studied. Thirty-five riding horses were used. Equine conformation was estimated by 24 indices. Rider oscillation was measured by an accelerometer fixed at the rider's waist. The spatial position of the oscillation was estimated by a double integration of the acceleration. Horses were evaluated for therapeutic riding by a Riding for the Disabled Association instructor as a rider. Evaluations were on a scale of 1 to 5, with 5 being the highest score for 27 items. Horses were classified into 4 groups: the short and narrow (SN), short and wide (SW), tall and narrow (TN), and tall and wide (TW). The frequencies of rider oscillation both at walk and trot were higher (P<0.01), and the vertical (P<0.01) and longitudinal (P<0.05) amplitudes at trot were smaller, on short horses than on tall horses. The vertical amplitude at walk was smaller (P<0.05) and the lateral amplitude at trot was larger (P<0.01) on wide horses than on narrow horses. Short horses could be used for the rider who requires side walkers. Wide horses could be used for relieving muscular tension and for the rider who could not maintain good balance on the horse. Short and wide horses should be suitable for therapeutic riding.

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 (123)I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's 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 Parkinson's disease. .