In this independent clinical study, we analyzed retrospectively the clinical features of 9 cases (6 male and 3 female) of Lambert-Eaton myasthenic syndrome that were administered 3,4-diaminopyridine (3,4-DAP). Four cases showed no cancer and 5 cases had small cell lung carcinoma. Seven cases were positive for anti voltage-gated calcium channel antibodies. Activities of daily living (ADL) were improved by 3,4-DAP in 8 cases that showed mainly weakness of the extremities, but did not improve ADL in 1 case with cerebellar ataxia of paraneoplastic cerebellar degeneration (PCD). Seven cases showed autonomic symptoms, and 6 cases were improved with 3,4-DAP. The maintenance dose varied widely among individuals, with a single dose ranging from 10 to 40 mg. Each patient was prescribed a maintenance dose 3 to 7 times a day. The daily dosage ranged from 36 to 100 mg. Two cases showed adverse effects to the treatment. Of those 2 cases, 1 case treated at 45 mg/day discontinued treatment, but another case treated at 100 mg/day reduced the dosage and continued treatment. The administration period was 1 to 149 months. Three cases have continued 3,4-DAP for more than 10 years. Four cases have discontinued 3,4-DAP, with 2 cases discontinuing due to death, 1 case discontinuing due to progression of cancer, and 1 case discontinuing due to an adverse reaction. Our results suggest that 3,4-DAP treatment is effective for weakness and autonomic symptoms, but may be ineffective for ataxia of PCD. Treatment with 3,4-DAP can be tolerated for a long period, but the optimal dosage varies widely among individuals.
The rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream-enacting behaviors related to the loss of the normal generalized skeletal muscle atonia during REM sleep, and shows REM sleep without atonia (RWA) during polysomnography (PSG). Patients with idiopathic RBD have been known to have a siginificantly increased risk of developing one of the α-synucleiopathies later in life, therefore the diagnosis of RBD is very important and must be dealt with carefully. A 51-year-old man was identified presenting dream-enacting behaviors and unpleasant dreams suggesting the diagnosis of RBD, in addition to snoring and excessive daytime sleepiness. Attended video-PSG excluded RBD showing REM sleep with atonia and without increased phasic EMG activity, and diagnosed with severe obstructive sleep apnea (OSA) with an apnea-hypopnea index of 30.1 demonstrating that the reported abnormal sleep behaviors occurred only during respiratory event-induced arousals. Continuous positive airway pressure therapy eliminated the abnormal behaviors, unpleasant dreams, snoring and daytime hypersomnolence. This case shows that severe OSA mimic the symptoms of RBD and that attended video-PSG is necessary to establish the diagnosis of RBD, and identify or exclude other causes of dream-enacting behaviors.
A 58-year-old female was admitted to our hospital because of recurrent multiple cranial neuropathy (right facial palsy followed by involvement of the left trigeminal, facial, acoustic, pharyngeal, and vagal nerves and the right abducens nerve). Brain MRI showed gadolinium enhancement of the right abducens, bilateral facial/acoustic, and left pharyngeal/vagal nerves, and 18F-Fluorodeoxyglucose (FDG)-positron emission tomography revealed abnormal FDG uptake in the right facial, acoustic, pharyngeal, and vagal nerves and the left cervical lymph nodes. Blood and biochemical analyses did not show any abnormalities, including in the patient’s lactate dehydrogenase and soluble interleukin-2 receptor (sIL2R) levels. A cerebrospinal fluid (CSF) examination showed gradual increases in the patient’s cell counts and protein, β2-microglobulin, and sIL2R levels, but no malignant cells were detected. A thorough investigation involving repeated CSF examinations, whole-body computed tomography, bone marrow aspiration, random skin biopsies, and cervical lymph node aspiration biopsy examinations did not result in any definitive conclusions. Steroid therapy was ineffective, and the patient developed deafness in her left ear. Therefore, we performed a biopsy examination of the left acoustic nerve, which resulted in the patient being diagnosed with diffuse large B-cell lymphoma. High-dose MTX following the intrathecal administration of MTX, cytarabine, and prednisolone partially improved her symptoms, but she died after several episodes of clinical recurrence. Acoustic nerve biopsy may help diagnose neurolymphomatosis in carefully selected cases.
A 61-year-old man was admitted to our institution with progressive hypoacusia, double vision, and lightheadedness. Neurological examination on day 6 of his illness showed severe hypoacusia, mild confusion, ocular motility disorder, truncal ataxia and absence of a deep tendon reflex. MRI fluid-attenuated inversion recovery imaging revealed symmetrical high intensities in the tectum of the midbrain, involving the bilateral inferior colliculi and the bilateral medial thalami, which suggested Wernicke encephalopathy (WE). Thiamine was administered immediately after completion of the MRI, and the patients’ hearing and other abnormal neurologic signs improved rapidly within a few days, except for the absence of the deep tendon reflex. Whole blood examination at admission revealed very low levels of vitamin B1. The patient was discharged on day 19, and MRI on day 39 showed the disappearance of the abnormal high intensities involving the bilateral inferior colliculi. The present case indicates that hypoacusia and abnormal MRI signal due to WE might be normalized by administration of thiamine a few days after the onset of symptoms.
A 77-year-old man with a history of cigarette smoking had suffered from vertigo and depression repeatedly for twelve years. He gradually developed bradykinesia in the past half decade and fell down 3 times in the last half year. On admission, he presented with cerebellar ataxia and bulbar symptoms. Brain MRI showed atrophy in the cerebellum and brainstem. 123I-IMP SPECT showed hypoperfusion bilaterally in the cerebellum. Blood examinations showed various elevated inflammatory values and positive for HLA-B51. Cerebrospinal fluid (CSF) revealed aseptic meningitis and increased IL-6 levels. Therefore, we strongly suspected that he had chronic progressive neuro-Behcet’s disease (CPNBD), clinically. Systemic mucocutaneous symptoms appeared 1 month after starting treatments. Pathological findings of his skin biopsy were consistent with Behcet’s disease. It should be kept in mind that both positive HLA-B51 and increased CSF IL-6 levels have the possibility of containing important clues in the diagnosis of CPNBD.
A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3’ to 5’ DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.
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.
A 56-year-old man was sustained ticks at the left axilla and flank. He did not have a rash. About 3 months after the tick bites, he developed back pain, right leg weakness, right abducens nerve palsy, and left facial palsy. Western blot analysis for serum IgM and IgG antibodies against Borrelia were positive. We diagnosed Lyme borreliosis. The patient was treated with antibiotics and steroids, and the symptoms improved. Our findings demonstrate that, even if erythema migrans is not obvious, neuroborreliosis should be considered when neurological signs, such as multiple cranial nerve palsies, are present.
At 37 years of age, the patient initially presented with symptoms of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) during her 1st pregnancy. She was treated with intravenous immunoglobulin (IVIg), and showed favorable recovery, becoming almost asymptomatic by the age of 38. At 39 years of age, during her puerperal period of her second pregnancy, she developed symmetrical muscle weakness and sensory disturbance of the upper and lower limbs. Nerve conduction studies revealed diffuse demyelination of peripheral nerves, and she was diagnosed with recurrence of CIDP. Once again, she showed remarkable improvement after IVIg therapy, and she has remained asymptomatic without the induction of preventative therapies. Recurrence of CIDP triggered in accordance with multiple pregnancies is extremely rare, and its clinical and electrophysiological features are presented in this report.