Case Vignettes in Neurology

PATIENT CASE STUDIES

Case 29
Case discussion A six year old girl is being evaluated for slowly progressive loss of vision in her right eye of nine months duration. There are no other complaints. Her past medical history and development are normal. However, the child is repeating kindergarten. Her examination is significant for marked loss of visual acuity in the right eye. There is an anterior pupillary defect on the right, and funduscopic exam reveals optic atrophy. The child is hyperactive and she has a poor attention span. The remainder of her neurologic examination is normal. Examination of the skin reveals nine 5-10 mm hyperpigmented macules on the abdomen, trunk and extremities. She also has small hyperpigmented macules (freckles) in her axilla and groin. Review of the family history reveals that her father, paternal aunt, and paternal grandmother have similar skin lesions.
Summarize the Case in 1-2 sentences. A 6-year-old hyperactive girl with poor attention span presents with slowly progressive vision loss and an anterior pupillary defect on the right accompanied by optic atrophy. She also presents with hyperpigmented macules on the abdomen, trunk, extremities, axilla, and groin, and has a family history of similar skin lesions. good summary, what is the time course Discuss lesion localization on the basis of the physical examination. Cranial nerve 2 (optic nerve atrophy). Skin: hyperpigmented macules seen on the abdomen, trunk , extremities, axilla, and groin. good Discuss underlying pathogenesis on the basis of clinical course. The course is slowly progressive suggesting a degenerative (biochemical, metabolic) process or growing tumor. good Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses. Neurofibromatosis Type I (Von Reckling-Hausen's Disease) with optic glioma Alternative Diagnosis: Albright's syndrome (polyostotic fibroma, dysplasia, and precocious puberty) good; take one of the symptoms or signs and develop a classification of diagnoses around that; eg. optic nerve involvement could be secondary to 1. tumor optic nerve glioma 2. inflammation, optic neuritis 3. vascular, eg. recurrent ischemia to optic nerve to give a progressive course 4. toxins. eg. methano 5. metabolic. e.g. vitamin deficiency another way to look at the differential is to look at diseases that affect both nervous system and skin 1. phakomatosis eg tuberous sclerosis 2. ALD etc. Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis. Skin biopsy (H & E section): more than 20 melanin macroglobules per 5 high-power fields in "split" dopa preparations. MRI to visualize optic glioma. good; what about family hx Indicate complications of the disease and ancillary tests that would help evaluate them. She may develop hydrocephalus from aqueductal stenosis, epilepsy, mental retardation, and plexiform neurofibromas which may undergo secondary malignant degeneration and become sarcomas. She may also develop a pheochromocytoma, ependymomas, meningiomas, and astrocytomas. Measurement of urinary catecholamines and their metabolites, metanephrine and VMA, for a pheochromocytoma. Localization can usually be made by CT, MRI, or ultrasound. A MRI would visualize the ependymomas, meningiomas, and astrocytomas. good. it is easier for me to read the answer if you list the complications with the test next to it. Discuss how the underlying pathophysiology is relevant in the management of this patient. Neurofibromatosis Type I is an autosomal dominant disorder. The NF1 gene on chromosome 17 encodes a protein, neurofibromin, which is a GTPase that modulates signal transduction through the p21 ras oncoprotein pathway. NF1 is a tumor-suppressor gene. A mutation of this gene will increase the risk of developing nervous system neoplasms, such as neurofibromas (composed of Schwann cells and fibroblasts) and other tumors such as optic gliomas (overproduction of glial cells compressing the optic nerve). A surgical solution may be necessary to prevent further growth of the optic glioma and vision loss. Because of the gene defect, genetic counseling is advised for the family. The patient's prognosis is uncertain and possibly serious because of the complications that can occur. very good answer.
Other version: Summarize the Case in 1-2 sentences. A 6-year-old hyperactive girl with poor attention span presents with slowly progressive vision loss for 9 months and an anterior pupillary defect on the right accompanied by optic atrophy. She also presents with hyperpigmented macules on the abdomen, trunk, extremities, axilla, and groin, and has a family history of similar skin lesions. ok Discuss lesion localization on the basis of the physical examination. Cranial nerve 2 (optic nerve atrophy). Skin: hyperpigmented macules seen on the abdomen, trunk , extremities, axilla, and groin. ok Discuss underlying pathogenesis on the basis of clinical course. The course is slowly progressive suggesting a degenerative (biochemical, metabolic) process or a slow growing tumor. ok Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses. Diagnosis: Neurofibromatosis Type I (Von Reckling-Hausen's Disease) with optic glioma Alternative Diagnosis for hyperpigmented macules: Albright's syndrome (polyostotic fibroma, dysplasia, and precocious puberty) Alternative Diagnosis for optic nerve atrophy: Inflammation- optic neuritis Vascular- recurrent ischemia to optic nerve to give a progressive course Toxins- methanol Metabolic- vitamin deficiency ok Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis. Skin biopsy (H & E section): more than 20 melanin macroglobules per 5 high-power fields in "split" dopa preparations. MRI to visualize optic glioma. Family history too many tests; stick to 2 Indicate complications of the disease and ancillary tests that would help evaluate them. Hydrocephalus from aqueductal stenosis- CT to visualize. Epilepsy- EEG. Mental retardation- IQ Test. Plexiform neurofibromas which may undergo secondary malignant degeneration and become sarcomas- Skin biopsy Pheochromocytoma- Measurement of urinary catecholamines and their metabolites, metanephrine and VMA. Localization can usually be made by CT, MRI, or ultrasound. Ependymomas, meningiomas, and astrocytomas- MRI to visualize tumors. good Discuss how the underlying pathophysiology is relevant in the management of this patient. Neurofibromatosis Type I is an autosomal dominant disorder. The NF1 gene on chromosome 17 encodes a protein, neurofibromin, which is a GTPase that modulates signal transduction through the p21 ras oncoprotein pathway. NF1 is a tumor-suppressor gene. A mutation of this gene will increase the risk of developing nervous system neoplasms, such as neurofibromas (composed of Schwann cells and fibroblasts) and other tumors such as optic gliomas (overproduction of glial cells compressing the optic nerve). A surgical solution may be necessary to prevent further growth of the optic glioma and vision loss. Because of the gene defect, genetic counseling is advised for the family. The patient's prognosis is uncertain and possibly serious because of the complications that can occur. good Another Version:
Summarize the Case in 1-2 sentences. A 6-year-old girl with a dozen or so cafe-au-lait spots distributed on the body and intertriginous areas and family history of similar skin lesions presents with progressive loss of visual acuity with optic atrophy in her right eye for 9 months. She is also hyperactive and doing poorly in school. good Discuss lesion localization on the basis of the physical examination. retardation and hyperactivity: cortex cafe au lait spots: skin, connective tissue loss of visual acuity: retina, optic nerve good Discuss underlying pathogenesis on the basis of clinical course. The 9-month progressive course suggests a degenerative process. ok Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses. Neurofibromatosis of von Recklinghausen type I comment: good Differential diagnosis: syndromes with cutaneous manifestations: tuberous sclerosis, Sturge-Weber syndrome causes of monocular blindness--retinoblastoma, optic neuritis, optic nerve glioma, nerve sheath meningioma, orbital tumors, retinal abnormalities causes of mental retardation--cerebral palsy, tuberous sclerosis, Sturge-Weber good Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis. slit-lamp examination: Lisch nodules are very suggestive of neurofibromatosis following patient to observe increased numbers of cafe-au-lait spots, skin tumors appearing in adolescence, neurofibromas. good; also dna testing Indicate complications of the disease and ancillary tests that would help evaluate them. mental retardation: IQ testing epilepsy: EEG stroke due to vascular lesions: treatment of hypertension, other risk factors for stroke, follow-up CNS tumors of CNS: MRI images of cranium, spine peripheral nerve neurofibromas: supportive care, early detection, excision of symptomatic tumors pheochromocytoma: 24h urine collection testing for VMA scoliosis and other bone abnormalities: radiology neoplasia: leukemia, neuroblastoma, thyroid carcinoma, MEN syndrome. *psychiatric, as consequence of disfigurement: psychiatric care, support good Discuss how the underlying pathophysiology is relevant in the management of this patient. Von Recklinghausen’s disease type I shows an autosomal dominant inheritance in about 50% of the cases, with the rest being sporadic. The genetic trait has been linked to chromosome 17. The pathogenesis is not known presently, but tissues derived from neural crest cells, including Schwann cells, melanocytes, endoneurial fibroblasts, and skin and connective tissue components proliferate excessively or function abnormally, producing numerous benign neoplasms in skin, peripheral nerve, and CNS. The mental retardation has been attributed to cortical dysgenesis, a congenital malformation of the cortex. Treatment by surgical excision of the tumors is indicated if the tumors produce disfigurement or neurological complications, such as compression. The patient should be monitored for life, since the disease is inevitably progressive. correction: the gene has been identified to be a protein named neurofibromin which is a tumor suppressor. It modulates signal transduction by activating Ras-GTPase activity. Note that RAS-GTP is an oncogene.