Masanori Kurihara

Novel De Novo KCND3 Mutation in a Japanese Patient with Intellectual Disability, Cerebellar Ataxia, Myoclonus, and Dystonia

Spinocerebellar ataxia 19/22 (SCA19/22) is a rare type of autosomal dominant SCA that was previously described in 11 families. We report the case of a 30-year-old Japanese man presenting with intellectual disability, early onset cerebellar ataxia, myoclonus, and dystonia without a family history. MRI showed cerebellar atrophy, and electroencephalograms showed paroxysmal sharp waves during hyperventilation and photic stimulation. Trio whole-exome sequencing analysis of DNA samples from the patient and his parents revealed a de novo novel missense mutation (c.1150G>A, p.G384S) in KCND3, the causative gene of SCA19/22, substituting for evolutionally conserved glycine. The mutation was predicted to be functionally deleterious by bioinformatic analysis. Although pure cerebellar ataxia is the most common clinical feature in SCA19/22 families, extracerebellar symptoms including intellectual disability and myoclonus are reported in a limited number of families, suggesting a genotype–phenotype correlation for particular mutations. Although autosomal recessive diseases are more common in patients with early onset sporadic cerebellar ataxia, the present study emphasizes that such a possibility of de novo mutation should be considered.

Frontal Phonological Agraphia and Acalculia with Impaired Verbal Short-Term Memory due to Left Inferior Precentral Gyrus Lesion

We report a patient with phonological agraphia (selective impairment of kana [Japanese phonetic writing] nonwords) and acalculia (mental arithmetic difficulties) with impaired verbal short-term memory after a cerebral hemorrhage in the opercular part of the left precentral gyrus (Brodmann area 6) and the adjacent postcentral gyrus. The patient showed phonemic paragraphia in five-character kana nonword writing, minimal acalculia, and reduced digit and letter span. Mental arithmetic normalized after 8 months and agraphia recovered to the normal range at 1 year after onset, in parallel with an improvement of the auditory letter span score from 4 to 6 over a period of 14 months and in the digit span score from 6 to 7 over 24 months. These results suggest a close relationship between the recovery of agraphia and acalculia and the improvement of verbal short-term memory. The present case also suggests that the opercular part of the precentral gyrus constitutes the phonological route in writing that conveys phonological information of syllable sequences, and its damage causes phonological agraphia and acalculia with reduced verbal short-term memory.

Aphasic status epilepticus preceding tumefactive left hemisphere lesion in anti-MOG antibody associated disease

INTRODUCTIONnAnti-myelin oligodendrocyte glycoprotein (MOG) antibodies have recently been associated with epilepsy with FLAIR hyperintense cortical lesions on MRI. Association between anti-MOG antibodies and epilepsy without detectable structural brain lesion on MRI is unknown.nnnCASE REPORTnA 48-year-old right-handed man with a four-and-a-half year history of anti-MOG antibody associated demyelinating disease presented with persistent global aphasia. Brain MRI showed no new lesion or cortical lesion in the left hemisphere. Electroencephalogram, magnetoencephalography, and brain perfusion single-photon emission computed tomography suggested epileptic foci in the left temporal and parietal lobes, and the patients aphasia transiently responded to intravenous diazepam, compatible with aphasic status epilepticus. Cerebrospinal fluid showed mildly elevated cell count and positive oligoclonal bands. The patient only partially responded to antiepileptic drugs but responded to steroid pulse therapy. Six months later, the patient again exhibited global aphasia. Brain MRI showed tumefactive white matter lesion in the left temporo-parietal lobes.nnnCONCLUSIONnAutoimmune epilepsy without obvious causative lesion on MRI can be seen in the course of anti-MOG antibody associated demyelinating disease. The subsequent emergence of tumefactive lesion closely located to the epileptic foci may suggest some association between autoimmune epilepsy and demyelinating lesions.

Longitudinally extensive vasogenic edema following spinal cord infarction

Although transient lesion expansion has been reported after spinal cord infarction, longitudinally extensive lesion expanding more than several vertebral segments is extremely rare. We report a 45‐year‐old man having spinal cord infarction with subsequent longitudinally extensive lesion expansion on magnetic resonance imaging (MRI) 10 days after the infarction. The length of T2 hyperintense lesion was four vertebral segments on initial MRI but enlarged to span 12 vertebral segments on subsequent MRI, with Lhermittes sign, but otherwise without neurological deterioration. The expanded lesion extended beyond the anterior spinal artery region with high apparent diffusion coefficient value in the acute phase but improved within 10 days after starting cervical collar, suggesting that lesion expansion was due to vasogenic edema. This case illustrates that transient longitudinal lesion expansion accompanied by spinal cord infarction can reach lengths of up to 12 vertebral segments. Caution should be exercised while interpreting MRI findings to avoid excessive treatment or secondary damage.

Isolated unilateral ptosis due to midbrain infarction

A 74-year-old man with a history of diabetes mellitus, dyslipidemia, and hypertension presented with sudden left ptosis. Neurological examination revealed no apparent ophthalmoplegia (Fig. 1a). Pupils were equal with normal pupillary light reflex and near reaction. Facial sweating was preserved. Subsequent slight diplopia was noted on rightward, upward, and downward gaze. Hess charts were compatible with slight left oculomotor palsy (Fig. 1b). Brain MRI showed small left paramedian midbrain infarction (Fig. 1c, d). Atherosclerotic change in the basilar artery was observed without significant stenosis of basilar or left posterior cerebral artery (Fig. 1e). Atherothrombotic or lacunar stroke of the anteromedial midbrain artery was suspected. Left ptosis gradually improved in two months. The levator palpebrae superioris muscles are innervated by the central caudal subnucleus of oculomotor nucleus. Despite the bilateral organization of this subnucleus, damage to the paramedian fascicle originating from this subnucleus can cause isolated unilateral ptosis with minimal extraocular involvement. Isolated unilateral ptosis due to ischemia is a clinical pitfall, and brain MRI should be considered.

Severe visual impairment and subclinical encephalitis preceding clinical signs of chondritis in relapsing polychondritis

A 71‐year‐old woman with a 6‐month history of relapsing bilateral anterior scleritis presented with severe right visual impairment due to posterior scleritis. Despite radiological signs of encephalitis, the patient and her family members noticed no cognitive decline. The patient subsequently developed slight auricular pain without any visual changes such as redness or swelling, which, however, showed increased uptake of 18F‐fluorodeoxyglucose on positron emission tomography. Auricular cartilage biopsy revealed perichondrial inflammation suggesting relapsing polychondritis. Steroid therapy improved her symptoms and radiological findings. This case illustrates that asymptomatic brain inflammatory lesions can precede clinical signs of chondritis in relapsing polychondritis, and that auricular cartilage biopsy should be considered even with mild auricular pain without apparent clinical findings of inflammation.

Familial amyloid polyneuropathy diagnosed by minor salivary gland biopsy

A 71-year-old man with a 2-year history of dysesthesia with a glove-and-stocking-type distribution without family history for peripheral neuropathies was referred to our hospital. Symmetrical disturbance of touch and pain sensation and signs suggesting autonomic dysfunction including frequent urination, impotence, constipation, and orthostatic hypotension were noted with mild distal muscle weakness. Given the sensory-dominant peripheral neuropathy, neuropathy accompanying Sj€ ogren’s syndrome was one of our initial differential diagnoses. Despite negative anti-SS-A and SS-B antibodies, chewing gum test revealed decreased salivation. Salivary scintigraphy showed decreased accumulation especially in bilateral parotid glands (Fig. 1a). Minor salivary gland biopsy then was performed, which revealed only small amount of lymphocytic infiltration. Instead, amyloid deposition was detected with lobular acini atrophy (Fig. 1b-d). Genetic testing revealed c.148G>A (p.V30M) mutation in the TTR gene confirming the diagnosis of familial amyloid polyneuropathy (FAP). Amyloid deposition in salivary glands without oral symptoms is reported to be common in FAP. However, it should be noted that FAP can also cause symptomatic amyloid deposition in salivary glands causing decreased salivation as illustrated in our patient’s scintigraphy and histopathology. Although FAP is typically an early-onset familial disease with autosomal dominant inheritance, FAP can be late-onset and sporadic without obvious family histories. This case illustrates that FAP can mimic Sj€ ogren’s syndrome and that salivary gland histopathology should be carefully examined. References

HIV Dementia with a Decreased Cardiac 123 I-metaiodobenzylguanidine Uptake Masquerading as Dementia with Lewy Bodies

Cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy is a promising biomarker for dementia with Lewy bodies (DLB). However, we experienced a patient with cognitive decline, parkinsonism, and a decreased MIBG uptake who turned out to have HIV dementia. Normal dopamine transporter single-photon emission computed tomography reduced the possibility of comorbid Lewy body pathology causing the patient’s parkinsonism. The decreased MIBG uptake was most likely due to postganglionic sympathetic nerve denervation, which can also be caused by HIV. This case further emphasizes the importance of excluding other causes of autonomic neuropathy, including HIV infection, before interpreting MIBG scans.

Repetitive Discharge in a Case of Isaacs Syndrome with Burning Sensation

A 66-year-old man consulted a physician with 1-and-ahalf-year history of a burning sensation in all of his extremities without muscle weakness or reduced sensation. Screening tests for neuropathy revealed slightly elevated hemoglobin-A1c but otherwise normal findings. A nerve conduction study (NCS) showed a normal amplitude and velocity, and the physician did not consult a neurologist. Four months later, the patient presented to our neurology clinic with worsening symptoms. Taking his history revealed frequent muscle cramps, and myokymia was noted in both calves, suggesting Isaacs syndrome. NCS showed abnormal repetitive discharges after compound muscle action potential, which were also found in the first NCS (Picture A). Serum anti-voltage-gated potassium channel (VGKC) antibodies were positive. Antiepileptic drugs and immunoadsorption plasmapheresis plus steroid pulse therapy were started, followed by oral prednisolone (30 mg/day), resulting in symptom improvement. A follow-up NCS after symptom improvement showed the near disappearance of abnormal repetitive discharges (Picture B). Isaacs syndrome is an autoimmune neurological disease typically presenting with frequent muscle cramps (1). However, a burning sensation can also be the initial complaint, as in our patient (2). NCS results, including a visual assessment of the wave, should be cautiously interpreted.

Optic neuropathy and decorticate-like posture as presenting symptoms of Bickerstaff’s brainstem encephalitis: A case report and literature review

A 72-year-old woman with a 10-day history of bilateral visual impairment after respiratory tract infection showed decorticate-like posture and progressive deterioration of consciousness leading to coma. Ophthalmoplegia was also noted and anti-GQ1b antibodies were positive, consistent with Bickerstaffs brainstem encephalitis. After intravenous immunoglobulin and steroid pulse therapy, her consciousness gradually improved. However, severe visual impairment at the level of hand motion was noticed, which gradually normalized after second steroid pulse therapy. Atypical findings including optic neuropathy and decorticate-like posture can be seen in patients with Bickerstaffs brainstem encephalitis, and early diagnosis is essential for adequate management.