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V ALVAREZ I HERNANDO J FERNÁNDEZ- TORAL Unidad de Genética Molecular, Hospital Central de Asturias, Celestino Villamil s/n, 33006 Oviedo, Spain Correspondence to: J L Fernández-Torre
[email protected] 1 Lupski JR, Wise CA, Kuwano A, et al. Gene dosage is a mechanism for Charcot-MarieTooth disease type 1A. Nat Genet 1992;1:29– 33. 2 Latta E, Hoo JJ. Trisomy of the short arm of chromosome 17. Hum Genet 1974;23:213–17. 3 Bartsh-SandhoV M, Hieronimi G. Partial duplication of 17p. Hum Genet 1979;49:123–7. 4 Magenis RE, Brown MG, Allen L, et al. De novo partial duplication of 17p (dup(17)(p12p11.2)): a clinical report. Am J Med Genet 1986;24:415–20. 5 Schrander-Stumpel C, Schrander J, Fryns JP, et al. Trisomy 17p due to a t(8; 17) (p23; p11.2) pat translocation. Case report and review of the literature. Clin Genet 1990;37:148–52. 6 Kozma C, Meck JM, Loomis KJ, et al. De novo duplication of 17p (dup(17) (p12ºp11.2)): report of an additional case with confirmation of the cytogenetic, phenotypic, and developmental aspects. Am J Med Genet 1991;41:446– 50. 7 Chance PF, Bird TD, Matsunami N, et al. Trisomy 17p associated with Charcot-MarieTooth neuropathy type 1A phenotype: evidence for gene dosage as a mechanism in CMT1A. Neurology 1992;42:2295–9. 8 Roa BB, Greenberg F, Gunaratne P, et al. Duplication of the PMp22 gene in 17 p partial trisomy patients with Charcot-Marie-Tooth type-1A neuropathy. Hum Genet 1996;97:642– 9. 9 King PH, Waldrop R, Lupski JR, et al. CharcotMarie-Tooth neuropathy phenotype produced by a duplicated PMP22 gene as part of a 17p trisomy-translocation to the X chromosome. Clin Genet 1998;54:413–16.
Bilateral vestibular failure as a unique presenting sign in carcinomatous meningitis: case report Bilateral vestibular failure is a rare, often unrecognised, clinical entity (0.6%–2% of all routinely performed electronystagmography), characterised by unsteadiness of gait
J Neurol Neurosurg Psychiatry 2001;70:702–710 and oscillopsia during head movements.1 The unsteadiness is due to loss of the vestibulospinal reflexes. It increases in darkness or when walking on uneven or soft ground—that is, when visual and somatosensory inputs, necessary for vestibular substitution, get compromised. Oscillopsia is an illusory movement of a stationary surrounding which occurs typically during locomotion as a result of a retinal slip due to an insuYcient vestibulo-ocular reflex. The diagnosis of bilateral vestibular failure can be supported clinically by the finding of an abnormal visuo-ocular reflex (doll’s eyes), and an abnormal gaze fixation with compensatory saccades during rapid head turns (the head thrust test). A bithermal caloric test or a rotational chair test confirms the diagnosis by demonstrating the absence of vestibular responses.1 Ototoxic drugs (for example, aminoglycosides) are the most common cause of bilateral vestibular failure, followed by sporadic multisystem degeneration, infectious meningitis, bilateral cerebellopontine angle tumours, and autoimmune disorders. Neuropathies (such as vitamin B12 deficiency, hereditary polyneuropathies, and sarcoidosis), sequential vestibular neuronitis, and bilateral Menière’s disease also often lead to bilateral vestibular failure.1–3 Bilateral vestibular failure due to leptomeningeal metastasis has been reported to occur as a part of the clinical picture of carcinomatous meningitis, including symptoms of increased intracranial pressure, multiple cranial and spinal nerve involvement, and changes in mental state.1 3 4 We report on a patient with carcinoma of the breast where rapidly progressive bilateral vestibular failure was the main and outstanding presenting symptom of leptomeningeal spread. A 73 year old woman was admitted because of progressive gait unsteadiness, bilateral tinnitus, and headache for 2 months.
Figure 1 T1 weighted brain MRI shows gadolinium enhancement of both VIIIth cranial nerves in the acoustic canal.
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Her history comprised ischaemic heart disease, hypertension, familial tremor, and left Bell’s palsy 10 years previously. In 1995 she was operated on for breast carcinoma. Two years later metastasis to the axilla was treated with chemotherapy. On admission the patient complained about bilateral tinnitus, more on the right, and severe unsteadiness of gait, up to inability to walk without aid. When sitting or lying she had no coordination problems. Examination disclosed an old left peripheral facial palsy with pathological synkinesias. The eyes were aligned in all gaze directions and their range of movement was full. There was no primary position, nor gaze evoked nystagmus by observation or while wearing Frenzel’s glasses. When performing the doll’s eyes test a broken vestibulo-ocular reflex was obtained. The head thrust test demonstrated corrective saccades during head rotation to either side. The visual dynamic acuity test performed by reading a Jaeger’s chart while oscillating the head of the patient at a frequency of 1 Hz,1 showed a drop of four lines of visual acuity, compared with the visual acuity while the head was static. These findings were indicative of vestibulo-ocular reflex insuYciency. No papilloedema or pyramidal signs were found. The ankle reflexes were absent and sensation to pinprick was decreased up to the ankles; the position and vibration sense were normal. Cerebellar functions were preserved, as judged by the finding of a normal smooth pursuit and saccades of eye movements, as well as fingernose and heel-knee testing. When standing, the patient tended to fall backwards and was unable to stand with her eyes closed. Her gait was severely atactic, without any side preference. T1 and T2 weighted MRI of the brain with gadolinium disclosed a bilateral abnormal enhancement of the VIIIth cranial nerves in the region of the internal acoustic canal, compatible with an inflammatory or infiltrative process of the nerve (fig 1 ). Electronystagmography showed bilateral caloric weakness of 100%. Ocular motility was within normal limits. No spontaneous, gaze evoked, or positional nystagmus was recorded. A dynamic posturography showed a combined vestibular more than visual pattern of instability. Pure tone audiometry, performed 2 months earlier, had shown a bilateral sensorineural hearing loss of 40 dB in all frequencies, with normal speech discrimination. Repeated audiometric testing showed a plateau decrease of 50 dB in both ears and decreased speech discrimination of 75% in the right ear (normal>90% ), indicative of retrocochlear nerve involvement. On lumbar puncture a clear CSF with 160 mm H2O opening pressure (normal 100–200 mm H2O) was obtained. Laboratory analysis of CSF showed 31 epithelial carcinomatous cells/mm3, increased protein content of 121 mg% (normal50 mg/d). Carcinoembryonic antigen (CEA) was raised (16.8 µg/l, normal
