GDF-15, a mitochondrial disease biomarker, is associated with the severity of multiple sclerosis.

GDF-15, a member of the transforming growth factor beta superfamily, regulates inflammatory and apoptotic pathways in various diseases, such as heart failure, kidney dysfunction, and cancer. We aimed to clarify potentially confounding variables affecting GDF-15 and demonstrate its utility as a mitochondrial biomarker using serum samples from 15 patients with mitochondrial diseases (MD), 15 patients with limbic encephalitis (LE), 10 patients with multiple sclerosis/neuromyelitis optica spectrum disorders (MS/NMOSD), and 19 patients with amyotrophic lateral sclerosis (ALS). GDF-15 and FGF-21 were significantly elevated in MD. GDF-15 and FGF-21 showed a good correlation in MD but not in LE, MS, and ALS. GDF-15 was potentially influenced by age in LE, MS/NMOSD, and ALS but not in MD. FGF-21 was not correlated with age in MS/NMOSD, ALS, LE, and MD. GDF-15 was not correlated with clinical features in LE or BMI or body weight in ALS. GDF-15 positively correlated with the Expanded Disability Status Scale (EDSS) in MS/NMOSD, while EDSS showed no correlation with age. In conclusion, the results revealed that GDF-15 may be influenced by EDSS in MS/NMOPSD and by age in LE, MS/NMOSD, and ALS but not in MD. Mitochondrial damage in MS/NMOSD is a potentially confounding variable affecting GDF-15.

Body Lateropulsion and Cerebellar Tremor in a Patient with Pontine Infarction.

Body lateropulsion is known to be caused commonly by lateral medullary lesions but rarely by pontine lesions. It is also known to be associated with lesions of the dorsal spinothalamic tract or ascending graviceptive pathways. We herein report the case of a 75-year-old woman presenting with contralateral lateropulsion and cerebellar tremor caused by pons infarction. To our knowledge, this is the first case report of pontine infarction causing both lateropulsion and cerebellar tremor. Our case may be helpful in anatomical studies of ascending graviceptive pathways.

Cerebral Venous Air Embolism due to a Hidden Skull Fracture Secondary to Head Trauma.

Cerebral venous air embolism is sometimes caused by head trauma. One of the paths of air entry is considered a skull fracture. We report a case of cerebral venous air embolism following head trauma. The patient was a 55-year-old man who fell and hit his head. A head computed tomography (CT) scan showed the air in the superior sagittal sinus; however, no skull fractures were detected. Follow-up CT revealed a fracture line in the right temporal bone. Cerebral venous air embolism following head trauma might have occult skull fractures even if CT could not show the skull fractures.

[A representative case of joint contracture as a main feature of AL amyloid deposits identified in the skeletal muscles].

A 68-year-old man, with a history of type 2 diabetes mellitus and chronic kidney impairment, had been suffering from progressive knee joint contracture and dysesthesia of the lower extremities for 4 years. When he walked, his knees remained bent owing to contracture of the knee joints. There was no evidence of muscle pseudohypertrophy, intramuscular nodules, or muscle weakness. Clinical examination revealed IgA λ M-protein, reticular high-signal intensity lesions demonstrated by magnetic resonance T2-short TI IR(STIR) imaging of the lower extremity muscles, and a mixture of neurogenic and myogenic changes demonstrated by needle electromyography. A biopsy specimen from the vastus lateralis muscle identified Aλ amyloid deposits around the vessels, establishing a diagnosis of amyloid myopathy based on systemic AL amyloidosis. This case demonstrated that joint contracture and reticular lesions shown by magnetic resonance STIR imaging of the muscles can alert the physician to consider muscle biopsy to investigate deposition of amyloid in the skeletal muscles even in the absence of muscle pseudohypertrophy or weakness, both of which are characteristic of amyloid myopathy.

Downbeat nystagmus associated with damage to the medial longitudinal fasciculus of the pons: a vestibular balance control mechanism via the lower brainstem paramedian tract neurons.

The paramedian tract (PMT) neurons, a group of neurons associated with eye movement that project into the cerebellar flocculus, are present in or near the medial longitudinal fasciculus (MLF) in the paramedian region of the lower brainstem. A 66-year-old man with multiple sclerosis in whom downbeat nystagmus appeared along with right MLF syndrome due to a unilateral pontomedullary lesion is described. In light of these findings, a possible schema for the vestibular balance control mechanism circuit of the PMT neurons via the flocculus is presented. Damage to the PMT neurons impaired the elective inhibitory control mechanism of the anterior semicircular canal neural pathway by the flocculus. This resulted in the appearance of anterior semicircular canal-dominant vestibular imbalance and the formation of downbeat nystagmus. From the pathogenesis of this vertical vestibular nystagmus, the action of the PMT neurons in the vestibular eye movement neuronal pathway to maintain vestibular balance was conjectured to be as follows. PMT neurons transmit vestibular information from the anterior semicircular canals to the cerebellum, forming a cerebellum/brainstem feedback loop. Vestibular information from that loop is integrated in the cerebellum, inhibiting only the anterior semicircular canal neuronal pathway via the flocculus and controlling vestibular balance.

[Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) in early-onset dementia].

By reviewing and collating data in a 2-step postal survey sent to all of the institutions for individuals with dementia in Ibaraki prefecture requesting information on early-onset dementia (EOD) cases, 617 subjects with EOD were identified. The estimated prevalence of EOD in the target population was 42.3 per 100,000. Of the illness causing EOD, vascular dementia was the most frequent followed by Alzheimer's disease, head trauma, dementia with Lewy body/Parkinson's disease with dementia, frontotemporal lobar degeneration, and other causes. On the other hand, hereditary diffuse leucoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white matter disease with variable phenotypes. The onset of symptoms is usually in the fourth or fifth decade, progressing to dementia with death within 6 years. Recently, several mutations of the colony stimulating factor 1 receptor encoded by CSF1R segregating HDLS were identified. Since clinical presentations varied substantially within and across families with HDLS, CSF1R mutation carriers may be present in clinical series of Alzheimer's disease, frontotemporal lobar degeneration, corticobasal syndrome, multiple sclerosis, CADASIL, Parkinson's disease and ischemic stroke with additional white matter changes, all causing EOD. In the differential diagnosis of EOD, we should always consider HDLS and if necessary perform CSF1R gene analysis.

A case of disseminated sporotrichosis treated with prednisolone, immunosuppressants, and tocilizumab under the diagnosis of rheumatoid arthritis.

We encountered a disseminated sporotrichosis patient with polyarthritis and progressive skin ulcers, who had been previously treated with prednisolone, tocilizmab, tacrolims, and cyclophosphamide under the diagnosis of rheumatoid arthritis in another hospital. Making the diagnosis of leukocytoclasticvasculitis based on the clinical observation of skin ulcers, we intensified immunosuppressive therapy. Unfortunately, the patient developed septic shock. Blood culture revealed that the pathogenic organism was sporothrixschenckii. Any case of intractable arthritis or skin ulcers, which does not improve, despite adequate immunosuppressive therapy, is likely to be suspicious of sporotrichosis.

A Japanese case with Nasu-Hakola disease of DAP12 gene mutation exhibiting precuneus hypoperfusion.

A 38-year-old Japanese man with Nasu-Hakola disease (NHD) had repeated pathological fractures and frontal lobe symptoms which developed when he was 18 and 26 years old, respectively. Neuropsychological testing showed memory impairment, and in particular, visuo-spatial memory at the age of 35. Furthermore, single-photon emission computed tomography revealed precuneus hypoperfusion. The patient later suffered prolonged convulsive seizures, which left him in a persistent vegetative state. Genetic testing confirmed a heterozygous mutation in the DAP12 gene (a single-base deletion of 141 G in exon 3) specific to NHD. Precuneus dysfunction might contribute to characteristic memory impairment of NHD.