[Neuroleptic Intolerance and Residual Mutism in a Young Woman with Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis].

We report a case of anti-NMDAR encephalitis and residual mutism in a 23-year-old woman who presented with neuroleptic intolerance. Admission to our department for investigation of her abnormal behavior revealed cerebrospinal fluid (CSF) positivity for anti-NMDAR antibodies, and the patient underwent immunotherapy. However, generalized tonic seizures developed, requiring mechanical ventilation in the intensive care unit. Antipsychotic drugs were also administered for involuntary movements and insomnia. Thereafter, a malignant syndrome of severe hyperCKemia (Max: 191,120 IU/L) and shock developed, requiring resuscitation and three sessions of hemodialysis. Subsequent rituximab therapy led to improvement, except for mutism, which had newly developed during resuscitation. Seven months after initial admission, the patient was discharged with independent gait. However, her mutism still persists. Temporary mutism has been reported to occur in this type of encephalitis, albeit rarely. The fact that remission was not observed in this case may have been due to cerebellar infarction occurring during resuscitation, but the true cause remains unclear. Malignant syndrome or rhabdomyolysis, as seen in this patient, has also sometimes been reported in this form of encephalitis when antipsychotic agents, especially dopamine receptor blockers, have been administered. Therefore, such agents should be administered with caution in patients with anti-NMDAR encephalitis. (Received August 17, 2023; Accepted October 24, 2023; Published March 1, 2024).

[How Can We Suspect a Preclinical Alzheimer's Disease Only Through History Taking and Neurological Examination?]

Investigations of clinical biomarkers for discovering a preclinical Alzheimer's disease (AD) remain behind those of CSF and PET biomarkers. Almost all of today's checklists for early detection of AD are not generally useful for recognizing preclinical AD. Conversely, activities of daily living or language ability should be evaluated. In addition, focusing on risk factors for onset of AD, such as living alone/social isolation, hearing loss, hyposmia, loss of teeth, body weight changes, apathy/depression, and their combination, is valuable for the clinical investigation of preclinical AD.

Weak gluteus maximus and weak iliopsoas with normal gluteus maximus: Two complementary new signs to diagnose lower limb functional weakness.

BACKGROUND AND PURPOSE: The diagnosis of functional neurological disorder should be actively made based on the neurological signs. We described two new complementary signs to diagnose functional weakness of the lower limb, "weak gluteus maximus (weak GM)" and "weak Iliopsoas with normal gluteus maximus (weak iliopsoas with normal GM)," and tested their validity. METHODS: The tests comprised Medical Research Council (MRC) examinations of the iliopsoas and GM in the supine position. We retrospectively enrolled patients with functional weakness (FW) or structural weakness (SW) who presented with weakness of either iliopsoas or GM, or both. Weak GM means that the MRC score of GM is 4 or less. Its complementary sign, weak ilopsoas with normal GM, means that the MRC score of ilopsoas is 4 or less, whereas that of GM is 5. RESULTS: Thirty-one patients with FW and 72 patients with SW were enrolled. The weak GM sign was positive in all 31 patients with FW and in 11 patients with SW, that is, 100% sensitivity and 85% specificity. Therefore, the complementary sign, weak iliopsoas with normal GM, was 100% specific for SW. DISCUSSION: Although 100% should be discounted considering limitations of this study, these signs will likely be helpful in differentiating between FW and SW in the general neurology setting. Downward pressing of the lower limb to the bed in the supine position is interpreted by the patient as an active movement exerted with an effort and might be preferentially impaired in FW.

[Non-cerebellar ataxias: posterior column-like ataxia and cerebellar-like ataxia].

Ataxia is not only due to cerebellar lesions, but also due to non-cerebellar lesions such as those in the brain, spinal cord, dorsal root (DR), peripheral nerve. In this article, optic ataxia is excluded and 'vestibular ataxia' is briefly referred. Non-cerebellar ataxias are generically called sensory ataxia or posterior column ataxia. However, since non-cerebellar lesions, e.g. frontal lobe lesions, may develop "cerebellar-like ataxia" (Hirayama, 2010). At the same time, non-posterior column lesions, e.g. parietal lobe lesion, can show "posterior column-like ataxia". From these viewpoints, I here describe various non-cerebellar ataxia in some disorders such as tabes dorsalis and sensory neuropathies and emphasize a role of a peripheral sensory input to the cerebellum via the DR ganglia and spinocerebellar tract for sensory ataxia because there is the International Consensus (2016) that the ataxia in Miller Fisher syndrome is suggested cerebellar-like clinicophysiologically.

[A case of idiopathic spinal cord herniation with incomplete Brown-Séquard syndrome].

A 50-year-old man was referred to our hospital with myelitis associated with a 10-months history of progressive muscle weakness in the left leg. Neurological examinations demonstrated diffuse muscle weakness of the left leg, touch hypoesthesia of the right leg, reduced pain sensation below the right nipple, left pyramidal sign, and urinary incontinence. On the basis of thoracic spinal MRI and thoracic CT myelography, revealing anterior displacement of the spinal cord and enlargement of the posterior subarachnoid space at the Th4 vertebral level, we diagnosed the patient as having idiopathic spinal cord herniation with incomplete Brown-Séquard syndrome. After microsurgical release of the spinal cord and subsequent covering of the anterior dural defect with an artificial dura mater, the symptoms improved without progression. Clinicians should consider spinal cord herniation as a cause of slowly progressive thoracic myelopathy with Brown-Séquard syndrome.

[What Is Clinical Competence and How Can We Acquire It?]

Clinical competence is the spirit to discover something useful for the diagnosis or management of patients in a clinical setting. It requires a lively interest in humanity, careful observations, and deductive abilities. To acquire clinical competence, it is most important to observe the patients' various phenomena plainly rather than theoretically. For easy reference, I present Charles Miller Fisher's favorite sayings and my related experiences.

[Nontechnical Skills for Neurology Residents].

"Nontechnical skills," such as resilience, communication, management, information literacy, and educational capability, are required to be an the effective neurologist. Neurology residents should learn nontechnical skills in their residency programs.

"Burnt-out" progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia.

Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by John Cunningham virus (JCV) infection; however, a growing number of PML patients now survive longer and achieve remission, largely due to the advent of combination antiretroviral therapy. Several reports have suggested that the pathology in such patients presents only chronic demyelination without characteristic cellular changes, being referred to as "burnt-out" PML. On the other hand, our knowledge of "burnt-out" PML is still substantially limited, especially in patients with non-human immunodeficiency virus infection. Here, we report a case of PML associated with idiopathic CD4+ lymphocytopenia (ICL) who presented with spontaneous remission and survived for 11 years after onset. Notably, postmortem examination revealed surprisingly broad "burnt-out" lesions lacking the classic histopathological findings. However, pathogenic JCV-specific DNA sequences was still present in the autopsied brain tissue. This case suggests that complete remission can be achieved with a persistent presence of JCV-specific pathogenic sequences, even after a catastrophic infection. Considering that there have been a few reported cases of PML with ICL with long survival, the long-term survival of our case may share a favorable immunological response that is unique to a subgroup of ICL.

[Intermittent Claudication Secondary to Spine and/or Spinal Cord Diseases].

Currently, intermittent claudication is classified into the vascular (mainly secondary to peripheral arterial disease) and neurogenic (mainly secondary to lumbar canal stenosis) types. Intermittent claudication due to spinovascular insufficiency (myelopathy) has rarely been reported since it was first described by J. Dejerine in 1894. However, currently, intrinsic (vascular diseases of the spinal cord) and extrinsic (disorders causing cervicothoracic cord compression) factors are implicated as contributors to this condition. No internationally accepted, transdisciplinary and standardized definition, technical terminology, and classification of intermittent claudication are currently available. I propose a new classification in this article. I have focused on intermittent claudication secondary to spine and/or spinal cord diseases, with regard to its epidemiology, symptomatology, and differential diagnosis.

[A case of transient global amnesia associated with painless myocardial infarction].

A 66-year-old woman with a history of hypertension complained about sudden short-term memory loss. On arrival to our outpatient clinic, she was alert and oriented and did not have chest pain or shortness of breath. Neurological and neuropsychological examinations were within normal limits. In light of a transient anterograde amnestic attack and no neurological focal deficit, we clinically diagnosed transient global amnesia (TGA). To confirm whether there was an intracranial lesion or not, diffusion-weighted MRI of the brain was performed, and revealed hyper-intense lesions in the left hippocampus and right corpus callosum. Consequently, the patient was admitted to our hospital on follow-up for suspected cerebral infarction. On day 1, laboratory tests indicated an elevated troponin I level, and electrocardiogram revealed an inverted T wave in the inferior leads. Coronary angiography on day 9 of admission demonstrated severe stenosis of the right coronary artery, leading to a diagnosis of non-ST elevation myocardial infarction. Although TGA itself typically has a favorable prognosis, clinicians should consider potential concurrent painless myocardial infarction in patients with TGA.

[Anticancer Drugs and the Nervous System].

This article reviews the clinical features of toxicity in the peripheral and central nervous systems from anticancer drugs, including conventional cytotoxic chemotherapy, biologics, and targeted therapies, and excluding newer immunotherapies (immune checkpoint inhibitors and chimeric antigen receptor T cells). Neurologic complications from chemotherapy can be substantially disabling to patients and are being seen with increasing frequency because patients with cancer therapy are living longer and receiving multiple courses of anticancer regimens with combinations and longer duration. Clinicians, including neurologists, must know treatment-related neurotoxicity since discontinuation of the offending agent or dose adjustment may prevent further or permanent neurologic injury.

[Hirayama Disease can be Caused by Loss of Attachment of the Cervical Posterior Dura to the Pedicle due to Immunological Abnormalities of the Dura and Posterior Ligaments: A New Hypothesis].

Hirayama disease is a rare and self-limiting cervical myelopathy related to neck flexion in adolescents, predominantly male, originally described by Hirayama in 1959 and until today reported worldwide. It characteristically presents with asymmetric distal upper extremity muscular weakness and atrophy without objective sensory disturbance or lower extremity involvement, which spontaneously halts within 3-5 years after onset with some sequelae. Neuroradiological and autopsy/neuropathological studies have shown that the condition is caused by chronic ischemic changes to the anterior horn cells of the lower cervical cord due to abnormal forward-shifting of the lower cervical posterior dura on neck flexion. Although the true pathomechanism of the dural changes is still unknown, various hypothetical theories have been formulated: "tight dural canal in flexion", "flexion myelopathy", "engorgement of the posterior venous plexus", and "disproportional growth between the vertebral column and the contents of the spinal canal during puberty" (Hirayama). However, rarity of the condition and asymmetric cord involvement cannot be explained with these theories alone. Combination of a "posterior epidural ligament [sparse at C6-C7] factor" proposed by Shinomiya , "loss of dorsal dural attachment from the pedicle even in neutral position in the MRI" pointed out by some neuroradilogists, and "pathological abnormalities of elastic and collagen fibers in the operatively-resected dura" reported by several spinal surgeons suggest that abnormal changes of the dura and posterior ligaments, as well as the existence of "myodural bridge" at C1-C2 described by some neuroanatomists, can cause the dural forward-shifting of the lower cervical cord. In addition to these mechanical factors, immunological abnormalities such as hyperIgEemia and upreguration of some cytokines and chemokines in serum/CSF of patients with Hirayama disease have been reported. Furthermore, immune cells comprise -17% of all cells in the dura in rats. In conclusion, although further immunological studies of the patient's cervical dura and surrounding structures are required, I propose, in addition to Hirayama's theory, a new hypothesis about the pathomechanism of Hirayama disease, "loss of dorsal dural attachment from the pedicle due to immunological abnormalities of the dura and posterior ligaments", which can resolve the remaining problems of the condition. (Received May 25, 2020; Accepted July 2, 2020; Published December 1, 2020).

Isolated Hypoglossal Nerve Palsy Due to an Osteophyte with Atlantoaxial Dislocation.

Isolated hypoglossal nerve palsy (IHP), or hypoglossal nerve palsy without any other neurological signs, is rare. We report a woman with atlantoaxial dislocation (AAD) who presented with IHP due to hypoglossal nerve compression by an osteophyte at the hypoglossal canal. A 77-year-old woman presented with speech difficulties and the feeling of a swollen tongue on the left side for 3 days. Her only neurological feature was left hypoglossal nerve palsy. She had been diagnosed with AAD 2 years before. Computed tomography (CT) and high-resolution magnetic resonance imaging (MRI) revealed the compression of the basicranial hypoglossal nerve at the external orifice of the hypoglossal canal by an AAD osteophyte which was causing IHP. IHP can develop due to hypoglossal nerve compression by an osteophyte from AAD. CT and high-resolution MRI revealed this rare mechanism of IHP.

Rotatory Vertigo Caused by a Small Hemorrhage in the Superior Temporal Gyrus.

Rotatory vertigo is known to have not only peripheral causes, e.g., Meniere's disease, vestibular neuritis, and benign paroxysmal positional vertigo, but also central causes, e.g., stroke, hemorrhage, and tumor. In most cases, central rotatory vertigo is caused by a lesion in the brainstem or cerebellum, but rare cases with a cerebral lesion have also been reported. We herin describe a unique case with acute rotatory vertigo following a small hemorrhage in the left superior temporal gyrus, which probably led to a dysfunction of the visual-vestibular system.

[Symptomatology of Disorders of the Cervical Spine].

Although advances in neuroimaging have result in great improvement in the diagnosis of cervical spine and cord disorders, it is still more difficult to localize symptoms in the cervical spine and cord than in the brain. Here, I discuss the following relatively new aspects in cervical spine and cord symptomatology: I. Headache and facial pain; II. Vertigo and dizziness; III. Peculiar hand symptoms due to high cervical spine and cord disorders; IV. Symptoms in the C3-C4 level; V. Postoperative C5 palsy; VI. Peculiar weakness due to lower cervical spine diseases; VII. False localizing sensory signs; VIII. Autonomic symptoms; and IX. Transient neurological deficits.

[A case of acute leukoencephalopathy induced by a combination of 5-fluorouracil and metronidazole].

We describe a 66-year-old woman who received folinic acid, leucovorin, fluorouracil and oxaliplatin for advanced rectal carcinoma. These drugs were initiated on day 1, and a pelvic abscess was identified on day 7. Piperacillin-tazobactam was initially administered, but was changed to ceftriaxone and metronidazole on day 14 on the basis of antimicrobial susceptibility testing. On the following day, the patient reported blindness, and MRI of the brain showed signal abnormalities in the splenium of the corpus callosum on DWI, suggestive of metronidazole encephalopathy. Although the total body exposure was 2 g, metronidazole was discontinued. The patient developed coma a few days later, and MRI of the brain on day 26 showed high signal intensity extensively involving the white matter in the cerebrum as well as the brainstem and cerebellum. She died 37 days after the initial administration of the chemotherapy. Pathological studies demonstrated decreased staining intensity in the myelin sheath and multiple vacuolar alterations, consistent with toxicity induced by metronidazole and fluorouracil. Care should be taken when administering a combination of these drugs, even if the total body exposure to each drug is limited.

[From 'Involuntary Movements' to 'Movement Disorders'].

Apart from the term 'involuntary movements', the term 'movement disorders' encompasses not only classical hyperkinesias but also hypokinesias including catalepsy or apraxia. It enables us to understand abnormal movements by their phenomena instead of by their localization. To advance the grasping of movement disorders, we discuss the clinical and pathophysiological features of abnormal movements in catatonia/catalepsy, anti-NMDAR encephalitis, paroxysmal dyskinesias, stiff person/leg syndrome, corticobasal degeneration/syndrome, and hysteria. Particular emphasis is placed on the roles of consciousness/unconsciousness, voluntariness/involuntariness, paroxysmal/sustained aspects, and cortical/subcortical networks.

[A case of primary central nervous system anaplastic lymphoma kinase positive anaplastic large cell lymphoma manifested as a unilateral pachymeningits].

There have been 23 reports of primary central nervous system anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma in the literature. Here we report the 24th case of a 40-year-old man who presented with occipital headache for one month. His contrast-enhanced brain MRI showed enhancement around the right temporal lobe, which suggested a diagnosis of hypertrophic pachymeningitis. He improved with steroid therapy. After discharge, however, he was readmitted with generalized convulsive seizures. Finally, he was diagnosed as primary central nervous system ALK-positive anaplastic large cell lymphoma by brain biopsy. Primary central nervous system lymphoma invading dura matter can rarely manifests as a unilateral pachymeningitis. Therefore, in case of pachymeningitis, we should pay attention to the possibility of infiltration of lymophoma with meticulous clinical follow-up.

Questionnaire survey on recruitment for Japanese Neurology Society.

Many claim that they do not have enough neurologists in Japan, but supply and demand of neurologists remains to be analyzed. To investigate the recruitment for the Japanese Society of Neurology (JSN), the subcommittee of JSN for education performed a questionnaire-based survey in 80 medical universities and 271 board-certified education facilities throughout Japan. The response rate to the questionnaire was 77.5% in medical universities and 42.4% in education facilities. It was shown that each department of neurology in university recruits average 2.2 doctors, while they supposed that more than 4 doctors to be recruited every year. The questionnaire survey included what measures JSN should take in order to promote recruitment for JSN.