Efficacy of Trihexyphenidyl on Apraxia of Eyelid Opening in Parkinsonism: A Case Report.

Apraxia of eyelid opening (AEO) is occasionally seen in Parkinson's disease (PD) or related diseases. However, many clinicians have trouble with the management of AEO by Parkinsonism. In this report, we describe a case of AEO in Parkinsonism improved by trihexyphenidyl (THP). The patient was a 64-year-old woman, who was previously healthy but developed bradykinesia. She was clinically diagnosed as PD due to an L-dopa challenge test, but no other detailed tests were performed. She started antiparkinsonian medications and her symptoms were improved at an early phase. However, her motor symptoms were gradually exacerbated over time, and antiparkinsonian medications were dosed up. At 69 years old, blepharospasm and AEO developed. Although other antiparkinsonian medications did not improve her AEO, THP cured AEO dramatically at 73 years old. In this report, we discuss a mechanism of AEO by Parkinsonism and the pathway of THP for the improvement of AEO.

Three Types of Demyelination, Perivenous, Confluent, and Perineuronal Nets-Rich in a COVID-19 Patient With Meningoencephalomyelitis.

Neurologic symptoms are common in COVID-19, and a variety of neuropathological changes have been reported. One of the important neuropathological findings is demyelination. However, the underlying pathogenesis of demyelination remained poorly understood. We witnessed a case of COVID-19 with distinct types of demyelination in the cerebrum, medulla oblongata, and spinal canal, who died of sepsis. The postmortem examination showed the solitary massive demyelination in the medulla oblongata. The massive lesion was filled with components of perineuronal nets. In the spinal canal, confluent demyelination in bilateral lateral and dorsal funiculi was detected over the entire length from C1 to S5, which was maximum at the level of cervical spinal canal stenosis. Demyelination in the cerebrum was mainly perivenular, and augmented in the area of lacunar infarcts and dilated perivascular spaces. Considering the distribution patterns of the following three types of demyelination, the traces of viral spreading could be highlighted. Discontinuous perivenous demyelination in the cerebrum showed the result of hematogenous spreading. Longitudinal confluent demyelination of the spinal cord should be the picturesque of the trace of axonal spreading. The distribution of demyelination was possibly modified by the underlying diseases, diabetes mellitus, hypertension, and spinal canal stenosis.

Case report: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion: an autopsy case.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion is a clinicoradiological syndrome characterized by transient neuropsychiatric symptoms and hyperintensity of the splenium of the corpus callosum on diffusion-weighted MRI. Although intramyelinic edema and inflammatory cell infiltration can be predicted by MRI, the pathology of the splenium of the corpus callosum remains unknown. We encountered a case of clinically mild encephalitis/encephalopathy with a reversible splenial lesion and hypoglycemia in a patient who died of sepsis, and an autopsy was performed. The postmortem pathological findings included intramyelinic edema, myelin pallor, loss of fibrous astrocytes, microglial reactions, and minimal lymphocytic infiltration in the parenchyma. Based on these findings, transient demyelination following cytotoxic edema in the splenium of corpus callosum was strongly considered a pathogenesis of "clinically mild encephalitis/encephalopathy with a reversible splenial lesion" associated with hypoglycemia, and it could be generalized for the disease associated with the other causes. As cytotoxic edema could be the central pathology of the disease, the recently proposed term cytotoxic lesions of the corpus callosum may be applicable to this syndrome.

Clioquinol Decreases Levels of Phosphorylated, Truncated, and Oligomerized Tau Protein.

The neuropathological hallmarks of Alzheimer's disease (AD) are senile plaques (SPs), which are composed of amyloid ß protein (Aß), and neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau protein. As bio-metal imbalance may be involved in the formation of NFT and SPs, metal regulation may be a direction for AD treatment. Clioquinol (CQ) is a metal-protein attenuating compound with mild chelating effects for Zn2+ and Cu2+, and CQ can not only detach metals from SPs, but also decrease amyloid aggregation in the brain. Previous studies suggested that Cu2+ induces the hyperphosphorylation of tau. However, the effects of CQ on tau were not fully explored. To examine the effects of CQ on tau metabolism, we used a human neuroblastoma cell line, M1C cells, which express wild-type tau protein (4R0N) via tetracycline-off (TetOff) induction. In a morphological study and ATP assay, up to 10 µM CQ had no effect on cell viability; however, 100 µM CQ had cytotoxic effects. CQ decreased accumulation of Cu+ in the M1C cells (39.4% of the control), and both total and phosphorylated tau protein. It also decreased the activity of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) (37.3% and 60.7% levels of the control, respectively), which are tau kinases. Of note, activation of protein phosphatase 2A (PP2A), which is a tau phosphatase, was also observed after CQ treatment. Fractionation experiments demonstrated a reduction of oligomeric tau in the tris insoluble, sarkosyl soluble fraction by CQ treatment. CQ also decreased caspase-cleaved tau, which accelerated the aggregation of tau protein. CQ activated autophagy and proteasome pathways, which are considered important for the degradation of tau protein. Although further studies are needed to elucidate the mechanisms responsible for the effects of CQ on tau, CQ may shed light on possible AD therapeutics.

[A case of asymptomatic Stanford type A aortic dissection with multiple perforator infarcts due to pseudointracavitary thrombus].

A 56-year-old man presented to our hospital as he presented progressive hemiplegia of the right upper limb with no other symptoms, including chest pain. Inter-arm blood pressure difference was not observed. Laboratory investigations revealed an elevated D-dimer value (2.4 µg/ml). Chest X-ray study showed normal findings without widened mediastinum. Brain MRI showed acute multiple brain infarcts in the left posterior limb of the internal capsule and right pons on diffusion-weighted imaging. Bilateral internal carotid arteries were non-occlusive in MRA. Carotid duplex ultrasonography revealed normal internal carotid artery flow velocities bilaterally. Because ischemic lesions were found in multiple vascular territories, and D-dimer value was elevated, the patient underwent thoracic contrast-enhanced-CT to exclude malignant tumors. Stanford type A aortic dissection limited to the ascending aorta was detected. As the plaque had accumulated in the false lumen, we suspected that plaque in the false lumen could be an embolic source. After ascending aortic replacement surgery, brain infarction did not recur during hospitalization. In cases of ischemic stroke wherein multiple vascular territories are detected, and D-dimer value is elevated, even in patients without chest pain, the possibility of painless Stanford type A aortic dissection should be ruled out as an embolic source.

[A case of post-surgical inflammatory neuropathy with lower-extremity weakness after surgery for anorectal malignant melanoma that showed the effectiveness of immunotherapy].

A 59-year-old man with past histories of bronchial asthma and chronic sinusitis underwent transanal resection of anorectal malignant melanoma with general anesthesia. On the third day after surgery, he presented with subacute weakness with right dominant hypoesthesia in the bilateral lower limbs. Tendon reflexes were diminished without pathological reflexes. Blood examination showed increased eosinophils (2,058/µl) and elevated serum immunoglobulin E (675.0 IU/ml). Cerebrospinal fluid examination showed elevated protein (200 mg/dl) without pleocytosis (<5/µl). A nerve conduction study suggested multiple mononeuropathy with motor and axonal dominance in the right tibial, peroneal, and sural nerves. Because of eosinophilia and his past medical history (i.e., bronchial asthma and chronic sinusitis), we initially suspected eosinophilic polyangiitis granulomatosis (EGPA) as the cause of postoperative polyneuropathy. However, his neurological symptoms did not improve despite the decreased eosinophil count after tumor resection, which was inconsistent with EGPA. We biopsied the left sural nerve to exclude EGPA and make a diagnosis. Pathological findings revealed no demyelination, axonal degeneration, or eosinophil infiltration with granuloma formation; however, lymphocyte-dominated inflammation was observed around the epineurial small vessels. Thus, the patient was diagnosed with early onset post-surgical inflammatory neuropathy (PIN) based on his clinical course and the pathological findings. On post-surgery day 48, oral administration of prednisolone (40 mg/day) was started. His neurological symptoms improved quickly and remarkably. Our case suggests that, when multiple mononeuropathy develops early after surgery, PIN should be considered as a differential diagnosis to initiate appropriate treatment based on the pathological condition of neuropathy.

A case of longitudinally extensive transverse myelitis with an isolated pontine lesion following epidural and spinal anesthesia for cesarean section.

Severe neurologic complications following epidural and spinal anesthesia rarely occur. Transverse myelitis has been reported as a rare complication of epidural or spinal anesthesia. We report a case of longitudinally extensive transverse myelitis and an isolated pontine lesion, which responded to immunotherapy. The patient was a 31-year-old pregnant woman who underwent elective cesarean section under epidural and spinal anesthesia. Though the insertions of the epidural and spinal catheters were smooth, she experienced back pain and transient hearing loss during epidural anesthesia. Postoperatively, she exhibited severe motor weakness in both lower extremities, neuralgia below the level of Th10 dermatome, and urinary retention. Magnetic resonance imaging showed longitudinally extensive transverse myelitis from T6 to T10 with a ring-shaped enhanced lesion and an isolated pontine lesion. These findings on magnetic resonance imaging were suggestive of autoimmune diseases such as neuromyelitis optica. The patient was diagnosed with an immunoreactive disease triggered by epidural or spinal anesthesia and was administered high-dose methylprednisolone, which led to the improvement in clinical symptoms. Clinicians should be aware of the possibility of the development of longitudinally extensive transverse myelitis and isolated pontine lesions after cesarean section under epidural and spinal anesthesia.

[Spinal dural arteriovenous fistula presented with rapidly progressive myelopathy, longitudinally extensive spinal cord lesion, pleocytosis with polymorphonuclear predominance, and decreased cerebrospinal fluid glucose levels: a case report].

A 75-year-old woman developed low back pain, weakness of the lower extremities, and urinary retention. On day 7 after the onset of symptoms, she was brought to the emergency department of our hospital by an ambulance because of progressive weakness of both lower extremities. Spine MRI showed longitudinally extensive spinal cord lesion (LESCL) at the Th8-Th11 spinal cord level and flow voids around the lesions. Lumbar puncture revealed a normal opening pressure, yellowish appearance, pleocytosis with polymorphonuclear predominance, and decreased cerebrospinal fluid (CSF) glucose levels. Based on the rapidly progressing myelopathy, LESCL, and CSF findings, we initially diagnosed the patient with myelitis and administered acyclovir and high-dose intravenous immunoglobulin on day 7. Spine MRI with gadolinium-enhancement showed longitudinally extending flow voids of the thoracic cord, and digital subtraction arteriogram (DSA) revealed arteriovenous shunt on the dura with dilated and tortuous intradural veins. We finally diagnosed her with spinal dural arteriovenous fistula (SDAVF). Cases of SDAVF might be initially misdiagnosed as myelitis because of showing rapid progressive myelopathy, pleocytosis with polymorphonuclear predominance, and decreased CSF glucose levels. Lumbar puncture and steroid administration for the cases of SDAVF could aggravate the patient's neurological symptoms. Therefore, lumbar puncture and initiation of immunotherapy should be avoided until SDAVF is completely excluded in patients with suspected myelitis on spine MRI without gadolinium-enhancement, even if their neurological symptoms progress rapidly.

Mucosal large cell neuroendocrine carcinoma of the head and neck regions in Japanese patients: a distinct clinicopathological entity.

BACKGROUNDS: Large cell neuroendocrine carcinoma (LCNEC) is well-known as a lung cancer subtype. This study assessed the prevalence of head and neck mucosal LCNEC (M-LCNEC). METHODS: M-LCNEC was studied clinically, histologically and immunohistochemically. RESULTS: Of 814 surgically resected cases of mucosal head and neck carcinoma, only eight cases (0.98%; all men, mean age 64.6 years) were rediagnosed as M-LCNEC. They occurred in the oropharynx (n=3), larynx (n=4) and hypopharynx (n=1). Seven of the cases had regional lymph node metastases and four resulted in death. Histologically, M-LCNEC had a sheet-like trabacular organoid growth pattern of relatively large basaloid cells in which central necrosis, rosette formation, peripheral palisading and high mitotic figures were evident. M-LCNEC was immunopositive for two or three neuroendocrine markers (CD56, chromogranin-A and synaptophysin). All cases showed high proliferative activity. CONCLUSION: M-LCNEC in the head and neck regions is a distinct histopathological entity whose positivity for neuroendocrine markers makes its diagnosis important. As about half of the patients died of the disease, M-LCNEC has a relatively poor prognosis.