C entral nervous system (CNS) manifestations of systemic lupus erythematosus are highly diverse and often have major prognostic consequences. 1,2 The prevalence rate of nervous system involvement in SLE is approximately 50%, although the range is large, varing from 18% to 75% of SLE patients. 3,4 Neuropsychiatric manifestations, such as psychosis and seizures, are common in SLE. However, neurogenic bladder has rarely been reported in this disorder. Most patients in previous reports have CNS lupus with an upper neuron disorder presenting as a symptom of transverse myelopathy. 5,6 We describe the clinical feature of a female patient with neurogenic bladder accompanied with NPSLE of obvious diffuse cortical dysfunction without evidence of spinal cord involvement. CASE REPORTA 24-year-old woman was admitted because of voiding difficulty and malar rash for 2 months. She had alopecia, diffuse abdominal pain, fever, and abnormal behavior with tremor and agitation. A neurologic examination showed impaired cognitive function (mini-mental state examination 19/30) despite alert mentality. There was no evidence of sensory or motor deficit.Her initial laboratory findings showed; white blood cell: 4720/mm 3 (lymphocyte 283/mm 3 ), hemoglobin: 7.2 g/dL, platelets: 204,000/mm 3 , and markedly decreased C3 and C4: ͓19 mg/dL (normal, 90 -180 mg/dL) and 3 mg/dL (normal, 9 -37 mg/dL), respectively͔. Urine analysis revealed no RBC, white blood cell, or casts. Repeated urine cultures were negative. Antinuclear antibody (ANA, Ͼ1:2560, speckled type), antids DNA antibody (23.5 IU/mL, normal Ͻ7 IU/mL), anti-Ro antibody, anti-La antibody, and antiSmith antibody were positive. Anticardiolipin antibody and lupus anticoagulant were negative. Lumbar puncture showed a clear, colorless cerebrospinal fluid. Analysis of this cerebrospinal fluid showed normal results-protein, 30 mg/dL; glucose, 63 mg/dL; cell count,1/ L; IgG, 23 mg/dL (serum IgG, 3692 mg/dL); adenosine deaminase 1.5 U/L; and negative oligoclonal band. A 24-hour urine had 1079 mg of protein. A renal biopsy was performed and showed membranous glomerulonephritis.For evaluation of abdominal pain and obstruction of the urinary tract, abdominal computed tomography was undertaken and demonstrated diffuse bowel wall thickening in the proximal jejunal loop without hydronephrosis and abnormality of the bladder. Electroencephalogram was normal. Brain magnetic resonance imaging showed no abnormality except diffuse cortical atrophy and ventricular dilatation. To rule out myelopathy, electromyography and nerve conduction velocity were performed, and revealed no evidence of myelopathy. Therefore, spine magnetic resonance imaging was not done. Cardiovascular autonomic nervous function test, including heart rate variation in deep breathing, valsalva maneuver, and orthostatic change, showed abnormality.On urodynamic study, the volume of residual urine was 1100 mL and less than normal activity of detrusor muscle and flaccid bladder was seen. Because she did not have a voiding sense, free flowmetry ...

Genome sequencing is often pivotal in the diagnosis of rare diseases, but many of these conditions lack specific treatments. We describe how molecular diagnosis of a rare, fatal neurodegenerative condition led to the rational design, testing, and manufacture of milasen, a splice-modulating antisense oligonucleotide drug tailored to a particular patient. Proof-of-concept experiments in cell lines from the patient served as the basis for launching an "N-of-1" study of milasen within 1 year after first contact with the patient. There were no serious adverse events, and treatment was associated with objective reduction in seizures (determined by electroencephalography and parental reporting). This study offers a possible template for the rapid development of patient-customized treatments. (Funded by Mila's Miracle Foundation and others.) R are diseases in aggregate affect approximately 30 million persons in the United States alone. 1 Although next-generation sequencing is revolutionizing their diagnosis, the sheer number of distinct conditions (more than 7000 [https://globalgenes . org/ rare -list]) and the limited number of patients affected by each rare disease present major challenges for drug development.This report shows a path to personalized treatment for patients with orphan diseases. It describes the identification of a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (CLN7, a form of Batten's disease), a rare and fatal neurodegenerative disease. 2,3 Identification of the mutation was followed by the development and clinical deployment, within 1 year, of a tailored drug to treat the patient (Fig. 1A). Clinic a l Pr esentationA 6-year-old girl presented with the insidious onset of blindness, ataxia, seizures, and developmental regression. The parents' first concerns dated back to when the girl was 3 years of age, when her right foot began to turn inward. When she was 4 years of age, her family noticed her pulling books close to her face at bedtime. At 5 years of age, she came to medical attention because of modest language and social regression, as well as increased clumsiness and stumbling. In the months before she turned 6 years of age, the progression of symptoms accelerated, and she wasThe authors' full names, academic degrees, and affiliations are listed in the Appendix.

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