Frontotemporal lobar degeneration (FTLD) with ubiquitin/TDP-43-positive inclusions (FTLD-TDP) and Pick's disease are two major pathological substrates in sporadic FTLD patients. Although identifying these underlying pathologies during the life of the patient is crucial for specific pathology-based treatment in the future, adequate clinical data to infer pathologies are not available. Several recent studies demonstrated that Pick's disease cases tend to present clinically with frontotemporal dementia (FTD) or progressive non-fluent aphasia as the first syndrome, while sporadic FTLD-TDP cases frequently show semantic dementia. Some asymmetric motor disturbances (e.g., pyramidal signs, parkinsonism, and contracture) are frequent in sporadic FTLD-TDP during the course, but rare in Pick's disease. On the other hand, several previous studies have demonstrated that the most frequent first syndrome of FTLD-TDP with progranulin gene (PGRN) mutations is FTD and that neuronal loss in the frontal cortex is more severe than that in the temporal cortex. Therefore, it is plausible that the clinicopathological features of sporadic FTLD-TDP are different from those of Pick's disease and FTLD-TDP with PGRN mutations. Given that in vivo Aβ imaging will soon be put to practical use, clinical data useful for clinical differentiation of pathological subtypes of FTLD besides AD with atypical cerebral atrophy will be essential in the future.
This review deals with clinical features of multiple system atrophy (MSA), especially on natural history, sleep disordered breathing, and nocturnal sudden death, based on our recent analyses of definite MSA which we experienced in our institute. Fiberoptic laryngoscopic examination performed under propofol anesthesia revealed that upper airway obstruction is caused not only by vocal cord abductor paralysis but also by various mechanisms including floppy epiglottis and stenosis at the arytenoids during inspiration. We must be cautious not to exacerbate upper airway obstruction by continuous positive airway pressure (CPAP), which is now increasingly used to treat sleep disordered breathing of MSA. Our analyses also demonstrated that nocturnal sudden death was the most frequent cause of death in our MSA cohort, and CPAP could not be a prophylactic measure against sudden death. In order to prevent nocturnal sudden death, a new project is now under way using non-invasive positive airway pressure ventilation (NPPV) and/or artificial ventilation associated with tracheostomy.
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 onset 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.
We report a 67-year-old man who presented sudden loss of temperature sensation associated with hyperalgesia in the left trunk and extremities. No abnormal lesions were found on routine magnetic resonance image (MRI) in the brain and spinal cord. He did not show common manifestations of the lateral medullary syndrome including vertigo, nystagmus, ataxia, Horner's syndrome and ipsilateral facial sensory loss. We however suspected this syndrome, because he complained of characteristic, severe pain and electrical sensations in one side of his body. Re-examined, thinly sliced T2-weighted MRI showed a very small high intensity spot in the right medulla, corresponding to the location of lateral spinothalamic tract. Oral carbamazepine was partially effective to ameliorate the intractable central poststroke pain.
A 34-year-old man was admitted with his unsteady gait, difficulty in speech and a paroxysmal severe headache accompanied with sensori-motor disturbance of the right extremities and aphasic symptom. His family history was unremarkable. His unsteadiness has progressed very slowly from childhood. He noted to be inarticulate at the age of 18 years. At the age of 33 years, he suddenly had an attack of severe throbbing headache, which was mainly left parietal, with nausea and photophobia. During the headache, his right extremities were paralyzed and he became aphasic. He had lost a partial memory of the event. All these symptoms had gone within 24 hours. Thereafter, the same headache occurred about once a month. Neurological examination revealed a mild truncal ataxia and ataxic dysarthria. Electroencephalography (EEG) showed intermittent delta waves restricted over the left fronto-temporal region. Brain MRI showed a moderate atrophy of superior cerebellar vermis and anterior cerebellar lobe. The diagnosis of sporadic hemiplegic migraine (SHM) with cerebellar ataxia was made. Our case was very similar to familial hemiplegic migraine (FHM) 1, of which some families are accompanied with transient amnesia, cerebellar ataxia and EEG abnormality. Although we did not detect any mutations in CACNA1A gene previously reported in FHM1, our case might share same pathogenesis with FHM1.
We present a 71-year-old woman with hereditary hemorrhagic telangiectasia (HHT) who at age 69, had undergone total gastrectomy because of repeated upper gastrointestinal bleeding. A day prior to admission she began to demonstrate abnormal behavior. Examination showed she was restless and had higher brain dysfunction. Triphasic waves were seen on EEG, and a high signal in the globus pallidus on T1-weighted MRI. Plasma NH3 level was increased after a meal. Abdominal CT scan showed vascular anomalies including a portohepatic vein shunt. She was diagnosed with portosystemic encephalopathy. After treatment with a low-protein diet, lactitol, and branched chain-amino acids, her clinical condition, plasma NH3 level after a meal, and EEG returned to normal. Because portosystemic shunt is rare in HHT, there have been few reports of portosystemic encephalopathy with this condition. However, with aging, the possibility of portosystemic encephalopathy increases because of age-related increases in portosystemic shunt volume.
The lactate levels in the cerebrospinal fluid (CSF) can be used to distinguish bacterial meningitis from aseptic meningitis. However, it is usually difficult to promptly measure the lactate levels. There are certain blood gas analyzers that can be used to easily and promptly obtain glucose and lactose data. We ascertained whether the lactate and glucose levels from CSF samples can be analyzed by blood gas analyzers, and we subsequently compared the data obtained with that measured at the laboratory. In this study, we measured the cell counts and the protein, glucose, and lactate levels in 62 CSF samples obtained from 51 patients. Of these 62 samples, lactate and glucose of 17 samples were also measured by a blood gas analyzer. There were no significant differences in the lactate and glucose levels between the data measured at the laboratory and that measured by the blood gas analyzer. In conclusion, we consider that rapid measurement of the lactate and glucose levels in CSF samples by blood gas analyzers can be considerably reliable in clinical practice.
We investigated the relationship between nasal flaring and SpO2 in 19 patients with Duchenne muscular dystrophy (DMD) and 26 patients with myotonic dystrophy (DM1). In DMD patients, nasal flaring was observed when SpO2 was lower than 96%, while it was not seen even at 82% of SpO2 in DM1. None of the DM1 patients could perform voluntary nasal flaring. Nasal flaring is a useful indicator of hypoxemia in DMD but not in DM1. It remains to be elucidated whether the lack of nasal flaring in DM1 patients is due to abnormal respiratory central mechanism or nasal muscle weakness.
We report a 71-year-old man who presented with acute right hemiparesis and aphasia. The admission CT and CT angiogram showed multiple small calcified emboli in branches of the left middle cerebral artery. The patient had shown no sign of improvement after intravenous thrombolytic therapy. Follow-up CT indicated acute multiple infarctions in the left middle cerebral artery area coincident with the calcified emboli. Carotid duplex sonography and cervical CT angiogram showed calcified plaque with ulceration at the origin of left internal carotid artery, which is the origin of those emboli. Since calcified cerebral emboli (CCE) are rare, it should be further investigated if intravenous thrombolysis is effective in CCE.