Multiple system atrophy variant with severe hippocampal pathology.

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi-quantitative analysis of anti-alpha-synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann-Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann-Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP-43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha-synucleinopathy in the pathogenesis of MSA.

[A case of conduction aphasia with specific jargon utterance].

We report a patient with bilateral hemispheric lesions caused by two episodes of cerebral infarction who exhibited conduction aphasia with unique jargon. The patient was an 84-year-old, right-handed man. Beginning after the second episode of cerebral infarction (defined as the time of symptom onset), neologistic jargon and an iterative pattern of phonemic variation became prominent, whereas phonological paraphasia and conduite d'approche were observed in the patient's overall speech. Therefore, the aphasia was characterized by the combination of conduction aphasia and neologistic jargon. At 27 months after symptom onset, the neologisms and iterative pattern of phonemic variation had disappeared, but a wide variety of phonological paraphasia and conduite d'approche persisted, clarifying the pathological features of the conduction aphasia experienced by this patient. The conduction theory (Kertesz et al., 1970) provides a convincing explanation for the mechanism of the onset of neologisms in the present case. Thus, we propose the existence of a symptomatic relationship between neologisms and phonological paraphasia.

Longitudinal Change of DAT SPECT in Parkinson's Disease and Multiple System Atrophy.

BACKGROUND: Both Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative disorder affecting striatonigral system. Although various lines of evidence demonstrate that dopaminergic neuron degeneration emerges before the onset of motor symptoms in PD, preclinical/prodromal progression of neurodegeneration is far less understood in MSA. OBJECTIVE: The aim of this study was to clarify the difference in the progression of dopaminergic degeneration in MSA and PD using dopamine transporter single-photon emission computed tomography (DAT SPECT). METHODS: We analyzed longitudinal data of the specific binding ratio (SBR), a measure of striatal radiotracer uptake, in DAT SPECT from 7 patients with MSA-C, 5 patients with MSA-P, and 18 patients with PD. We performed 2.7±0.7 scans with an interval of 9.85±6.00 months for MSA and 2 scans with an interval of 2.16±0.16 years for PD. RESULTS: The rate of SBR decline was faster in both subtypes of MSA compared with PD, but the value was similar between MSA-P and MSA-C. The estimated SBR at the onset of initial motor symptoms was lower in PD and MSA-P than in MSA-C, especially in the predominantly affected side. SBR of the predominantly affected side starts to decrease before the onset of motor symptoms in PD and MSA-P, whereas the initiation of SBR decline is around the onset in MSA-C individuals. The decline of SBR in the less affected side was not clearly shown before the onset in MSA-P or MSA-C. CONCLUSIONS: Our results suggest that the SBR in DAT SPECT analysis is an important pathophysiological marker reflecting the disease- and subtype-specific progression of dopaminergic degeneration in MSA and PD.

[Case of rapidly progressive syringomyelia due to a spinal hemangioblastoma].

A 35-year-old man came to the hospital showing signs of worsening dysesthesia on his right hand. The dysesthesia started on his right hand and then spread to his forearm in two months. It also appeared on his left hand transiently. Initial MR imaging revealed a high signal intensity lesion at Th1-Th10 with an irregular margin (presyrinx state) below C3 on T2WI. The legion extended up to the medulla oblongata rapidly. Corticosteroid therapy lead to a slight improvement in dysesthesia symptoms but did not last. Immunosuppressant was also ineffective. Further examination using Gd enhanced MR imaging in a neurosurgery clinic in a university hospital revealed a spinal tumor at the Th10 level. A tumor resection was performed and dysesthesia improved. Pathological analysis showed hemangioblastoma. Presyrinx and syrinx above Th1 disappeared after the operation. It is necessary to search the whole spine carefully for the possibility of a tumor in the case of steroid resistant progressive spinal lesions with an unknown origin. And we stress the importance of timely surgical intervention regardless of idiopathic or secondary syringomyelia. We would like to report this clinical course presenting MR imaging and discuss the mechanism of forming syringomyelia based on the hypothesis of the alteration of CSF flow.

[A patient with myelitis of varicella-zoster without skin lesions--diagnostic value of virus antibody index in CSF].

A previously healthy 55-year-old woman developed abnormal sensation on the right occipital region. It expanded for the following three weeks. On admission, examination revealed abnormal and decreased sensation in touch and pinprick at right C2 to C6 dermatome without skin lesion. There was no muscle weakness. Deep tendon reflexes were more active in the right than in the left. MRI demonstrated a lesion of isointensity on T1-weighted, hyperintensity on T2-weighted, which was enhanced with contrast material on gadolinium-enhanced T1-weighted image at the upper cervical spinal cord corresponding to C2. Laboratory studies showed no immunosuppression and autoantibodies. The antibody index to varicella-zoster virus (VZV) was elevated in the cerebrospinal fluid (CSF). This finding prompted us to a diagnosis of myelitis of zoster sine herpete. VZV is thought to be a causative agent in cases of CNS infections of unknown etiology such as myelitis, even in the absence of skin manifestations. Amplification of VZV DNA by PCR in the CSF and the detection of an intrathecal production of anti-VZV antibodies have important diagnostic value, although their presence depends on the timing of the CSF sampling. The percentage of PCR-positive cases drops after seven or ten days, whereas that of specific antibodies-positive cases elevates. Because VZV myelitis are usually protracted, PCR does not always provide an exquisite sensitivity. Thus, the evaluation of antibody index provides the evidence of intrathecal production of anti-VZV antibodies. That is expressed as CSF antibody titer/serum antibody titer/CSF IgG/serum IgG. This quotient superior to 1.5 or 2.0 suggests CNS synthesis. As the sample of our patient was taken relatively late, this value was diagnostic. We would like to emphasize the importance of making precise diagnosis and adequate initial treatment in patients with myelitis of unknown etiology even if there is no skin lesions.

Longitudinal MRI study of multiple system atrophy - when do the findings appear, and what is the course?

Several investigators have revealed features of multiple system atrophy (MSA) by magnetic resonance imaging (MRI). For use in clinical diagnosis, we determined the exact time when two main features of pontine and putaminal intensity changes appeared. Furthermore, in order to reveal the course from when the disorder first appeared and how it spread, we also investigated the course of MRI findings and differences between clinical subtypes. The cranial MRI of 42 patients with MSA were longitudinally studied including comments on the so called "cross sign" of pontine T2 high intensity, which was divided into 6 stages, and also on the linear T2 high intensity of the dorsolateral side of the putamen ("putaminal slit") which was divided into 4 stages. Patients were classified as 16 MSA-C, 7 autonomic dominant type (MSA-A), and 19 MSA-P. The age at onset ranged from 41 to 74 years (mean, 55 +/- 9). The duration of the disease in the MRI study ranged from 1 to 24 years. The pontine "cross sign" was completed (shows Cross, stage IV) earlier in MSA-C mainly before 5 years, later in MSA-P and even much later in MSA-A. Regarding the "putaminal slit", MSA-P shows earlier bilateral changes (stage II), mostly before 3 years, compared with MSA-C, which requires 4 years to reveal even a unilateral change (stage I), or MSA-A which requires even more time. MRI findings showed a tendency to relate to clinical findings, since MSA-C exhibits "cross sign" completion earlier than bilateral "putaminal slit"; however, MSA-P shows bilateral "putaminal slit" earlier than "cross sign", and MSA-A requires much more time to show both. Clinically, MSA-C, MSA-A, or MSA-P showed different MRI courses so that three subtypes could be defined also with MRI findings. Therefore these observations are useful not only for diagnosis of MSA itself, but also to distinguish clinical subtypes (MSA-C, MSA-A, or MSA-P) which have different rates of lesion progression.