Corticobasal degeneration with visual hallucination as an initial symptom: A case report.

Although the initial symptoms of corticobasal degeneration (CBD) are varied, psychiatric symptoms are uncommon. Here, we report the autopsy findings of a patient with early CBD who presented with hallucinations. A 68-year-old man developed memory loss and visions of bears and insects. Because of slow vertical eye movement, postural instability, and levodopa-unresponsive parkinsonism, the patient initially was clinically diagnosed with progressive supranuclear palsy. He died of a urinary tract infection 11 months after the onset of the disease. Histopathological examination revealed neuronal loss and gliosis, which were severe in the substantia nigra and moderate in the globus pallidus and subthalamic nucleus. Astrocytic plaques were scattered throughout the amygdala and premotor cortex. The superficial cortical layers lacked ballooned neurons and spongiosis, and tau deposition was greater in glia than in neurons. The amygdala contained a moderate number of argyrophilic grains and pretangles. Western blot analysis showed a 37-kDa band among the low-molecular-weight tau fragments. Because the CBD pathology was mild, we attributed the patient's visual hallucinations to the marked argyrophilic grain pathology. CBD can occur with psychiatric symptoms, including visual hallucinations, and argyrophilic grain pathology may be associated with psychiatric symptoms.

Atypical TDP-43 proteinopathy clinically presenting with progressive nonfluent aphasia: A case report.

Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.

Neuropathological analysis of cognitive impairment in progressive supranuclear palsy.

BACKGROUND: Cognitive impairment is an important symptom in progressive supranuclear palsy (PSP), but the pathological changes underlying the cognitive impairment are unclear. This study aimed to elucidate relationships between the severity of cognitive impairment and PSP-related pathology. METHODS: We investigated the clinicopathological characteristics of 10 autopsy cases of PSP, including neuronal loss/gliosis and the burden of PSP-related tau pathology by using a semiquantitative score in 17 brain regions. Other concurrent pathologies such as Braak neurofibrillary tangle stage, Thal amyloid phase, Lewy-related pathology, argyrophilic grains, and TDP-43-related pathology were also assessed. We retrospectively divided the patients into a normal cognition group (PSP-NC) and cognitive impairment group (PSP-CI) based on antemortem clinical information about cognitive impairment and compared the pathological changes between these groups. RESULTS: Seven patients were categorized into the PSP-CI group (men = 4) and three into the PSP-NC group (men = 3). The severity of neuronal loss/gliosis and concurrent pathologies were not different between the two groups. However, the total load of tau pretangles/neurofibrillary tangles was higher in the PSP-CI group than in the PSP-NC group. In addition, the burden of tufted astrocytes in the subthalamic nucleus and medial thalamus was higher in the PSP-CI group than in the PSP-NC group. CONCLUSION: Cognitive impairment in PSP may be associated with the amount of tufted astrocyte pathology in the subthalamic nucleus and medial thalamus.

[An autopsy case of polyarteritis nodosa accompanied with multiple immune-specific autoantibodies and rhabdomyolysis].

A 72-year-old male complained of fever lasting 1 month and developed muscle weakness and paresthesia in the legs. He presented with muscle weakness, grasping pain, decreased deep tendon reflexes in the extremities, and reduction of tactile sensation in the distal parts of the left leg muscles. Blood tests revealed leukocytosis and inflammatory reactions. Collagen-disease-specific autoantibodies including anti-double-stranded DNA and anti-Scl-70 antibodies were positive, but antineutrophil cytoplastic antibodies were negative. Nerve conduction studies revealed asymmetric axonal degeneration, indicating multiple mononeuropathy. We started intravenous methylprednisolone pulse and plasma exchange therapies. However, the patient developed intestinal necrosis and perforation, and he died 44 days after the onset of fever. An autopsy revealed vasculitis in small- to medium-sized vessels in multiple organs as well as myoglobin casts in the renal tubules, which were suggestive polyarteritis nodosa (PAN) accompanied with rhabdomyolysis. Positivity for collagen-disease-specific autoantibodies and accompanying rhabdomyolysis are atypical findings with PAN. This patient was not clinically diagnosed as PAN, and so promptly starting immunotherapies should be considered when a case presents with evidence of vasculitis.

An autopsy case of progressive supranuclear palsy. Pallido-nigro-luysian type with argyrophilic grains clinically presenting with personality and behavioral changes.

Pallido-nigro-luysian atrophy (PNLA) is a variant of progressive supranuclear palsy (PSP). Patients with PSP sometimes show psychiatric signs, but there are few reports about such signs being associated with PSP-PNLA. Here, we report a case of PSP-PNLA with argyrophilic grains (AGs) in a patient clinically diagnosed as having PSP-frontotemporal dementia (PSP-F). A 74-year-old man described as "kind" presented with impaired memory, irritability, and apathy. He showed levodopa-resistant parkinsonism and postural instability. Brain magnetic resonance imaging revealed mild atrophy of the midbrain and right-side-dominant atrophy of the hippocampus and temporal lobe. The patient was diagnosed as having PSP with frontal lobe cognitive or behavioral presentations (PSP-F). He died of aspiration pneumonia at age 81. At autopsy, macroscopic examination revealed depigmentation of the substantia nigra and grayish discoloration of the dentate nucleus, globus pallidus, and subthalamic nucleus. Severe gliosis was observed in the same regions. There were many phosphorylated tau-immunoreactive equivocal tufted astrocytes in the globus pallidus. Many neurofibrillary tangles and neuropil threads were observed in the substantia nigra and subthalamic nucleus, and few tau aggregates were observed in the frontal cortex. In contrast, AGs were abundant in the amygdala, entorhinal cortex, and anterior cingulate gyrus, with an asymmetric distribution. The pathological observations led us to change the diagnosis to PSP-PNLA with AGs. Although most cases of PSP-F derive from tau pathology in the frontal cortex, this patient did not have phosphorylated tau-immunoreactive aggregates in that location. Our observations suggest that the psychiatric signs of PSP-F should be considered as being due to the presence of limbic AGs, not frontal tau pathology.

First Japanese autopsy case showing LRRK2 mutation G2019S and TDP-43 proteinopathy.

This is the first Japanese autopsy case of Leucine-rich repeat kinase 2 (LRRK2) G2019S mutation with atypical TDP43 proteinopathy. Our case is important that presented clinically dysphagia and pathologically TDP-43 proteinopathy. TDP43 may play an important role of clinical presentation with LRRK2 G2019S mutation carriers.

An autopsy case of PARK2 due to a homozygous exon 2 deletion of parkin and associated with α-synucleinopathy.

Lewy bodies (LBs) are usually detected in patients with idiopathic Parkinson's disease (PD), but there have been few reports of LBs in a familial form of early-onset PD associated with several mutations in parkin, a gene that encodes a ubiquitin E3 ligase involved in mitochondrial homeostasis, being also known as PARK2. Here, we report a case of PD with a PARK2 mutation characterized by a homozygous deletion of exon 2 and incidental LB pathology. A 60-year-old man developed tremor in the upper limbs. Although levodopa was initially effective, his symptoms slowly progressed. His cardiac uptake of 123 I-metaiodobenzylguanidine, as assessed by myocardial scintigraphy, decreased from an early stage after the onset. At the age of 81 years, he developed Legionella pneumonia and died of respiratory failure. Histopathological examination revealed a moderate loss of pigmented neurons, as well as gliosis in the substantia nigra and the locus coeruleus. Little LB-related pathology was found in the locus coeruleus, dorsal nucleus of vagal nerve, and basal nucleus of Meynert. The cardiac sympathetic nerve in the epicardium showed a reduction in the numbers of fibers immunoreactive for tyrosine hydroxylase and phosphorylated neurofilament protein. Genetic analysis of frozen brain materials revealed a homozygous deletion of exon 2 of parkin. To our knowledge, this is the first autopsy case with a homozygous deletion of exon 2 of parkin. The number of LBs was small, the age of disease onset was later than that in typical PARK2-associated PD patients, and cardiac sympathetic denervation was also present. Thus, we considered the LBs in our case as incidental and preclinical α-synucleinopathy.

[Surgical considerations for two patients with cardioembolic stroke and mobile thrombus in the left atrium appendage].

Two men (Case 1, 74 years old; Case 2, 65 years old) developed cardioembolic stroke due to self-interruption of anticoagulants for treating atrial fibrillation. They both had mobile thrombus in the left atrial appendage. In Case 1, a left atrial thrombectomy was scheduled on day 8, but infarction re-occurred on the morning of the the surgery, producing neurological sequelae. In Case 2, left atrial thrombectomy and left atrial appendage closure were performed successfully on day 8. The indication and timing of cardiac thrombectomy after the onset of cerebral infarction have not been standardized, and they seem to differ among individuals. Therefore, in the future, the optimal timing of left atrial thrombectomy should be decided based on the size and morphology of the left atrial thrombus, the size of the cerebral infarction and the presence or absence of hemorrhagic infarction.