804 Letters, Correspondence, Book reviews have already been described to occur with Correspondence to: Dr D Michel, Service de Neu- some mutations. rologie, Hôpital de Bellevue, 42055 Saint-Etienne, There are only two previous reports Cedex 2, France. relating to three pairs of identical twins with CMT and known genetic defects. In the two 1 Goldsmith P, Rowe D, Jäger R, et al. Focal ver- pairs with the 17p11.2 duplication there was tebral artery dissection causing Brown- remarkable clinical variability.6 We have also Séquard’s syndrome. J Neurol Neurosurg Psy- seen a pair of identical twins with a P0 muta- chiatry 1998;64:415–16. 2 Gutowski NJ, Murphy RP, Beale DJ. Unilateral tion in whom there was marked variability in upper cervical posterior spinal artery syndrome early ages (unpublished data). Apart from the following sneezing. J Neurol Neurosurg Psychia- asymmetry of toe responses in one of the try 1992;55:841–3. probands, the genetically identical twins 3 Bergqvist CAG, Goldberg HI, Thorarensen O, et al. Posterior cervical spinal cord infarction described here are phenotypically very simi- following vertebral artery dissection. Neurology lar, suggesting that the expression of this 1997;48:1112–5. mutation was not influenced by other non- 4 Hundsberger T, Thömke F, Hopf HC, et al. genetic factors. Symmetrical infarction of the cervical spinal cord due to spontaneous bilateral vertebral Codon 39 seems to be of particular Sagittal T2 weighted MRI of the cervicodorsal artery dissection. Stroke 1998;29:1742. importance to Cx32 protein function as cord : high linear signal extending from C4 to 5 Masson C. Les accidents ischémiques médul- changing of the wild type amino acid has T5 vertebral levels. laires. Presse Med 1994;23:1723–8. caused CNS dysfunction in addition to the peripheral neuropathy. Moreover its expres- a predominantly right sided tetraparesia and Autonomic dysfunction and orthostatic sion does not seem to depend on non-genetic urinary retention. There was no history of factors, as might be expected in a hemizygous neck trauma. Cranial nerve examination was hypotention caused by vitamin B12 condition. normal. There was a right sided hemiplegia deficiency and a moderate left sided hemiparesis. Deep tendon reflexes were normal, right plantar Orthostatic hypotension sometimes is a WMJr was supported by grants from CAPES, reversible neurological complication of vita- FAPESP, and FAEPA (Brazil). response was extensor. There were bilateral spinothalamic problems below T4 with loss min B12 deficiency.12 Eisenhofer detected W MARQUES JR of touch sense in the right leg. Thus the deficient sympathetic catecholamine release M G SWEENEY in insulin tolerance testing,2 but the mech- NWWOOD examination was consistent with atypical, University Department of Clinical Neurology, right cervical Brown-Séquard’s syndrome. anism of orthostatic hypotension in vitamin Institute of Neurology, Queen Square, London, UK Biological investigations were normal. CSF B12 deficiency remains unclear. We report a protein was 0.34 g/l, glucose 2.54 mmol/l patient with vitamin B12 deficiency and S J WROE (2.10–4.20 mmol/l). There were 7 white cells reversible orthostatic hypotension, and dis- Department of Clinical Neurology, 3 Ipswich Hospital NHS Trust, Ipswich, UK and 25 red cells/mm . cuss the mechanism of this symptom. There were no oligoclonal bands. The A 77 year old man admitted to our hospital W MARQUES ECG was normal. There was no aortic had had unstable gait and urinary urgency for Department of Neurology, dissection shown on CT or MRI. Visual 6 months, clumsiness of the hands and School of Medicine of Ribeira˜o Preto, Brazil evoked potentials were normal. Somatosen- tingling sensations in the legs for 3 months, Correspondence to: Dr Nicholas Wood, Institute of sory evoked potentials were abnormal for the and, for a month, occasional dizziness on Neurology, Queen Square, London WC1N 3BG, standing. The dizziness was mild without any UK. Telephone 0044 171 837 3611 extn 4255; fax right lower limb at the cervical level. A sagit- 0044 171 278 5616. tal T2 weighted MRI showed linear cord high attack of syncope. He had no other symptoms signal from C4 to T5 vertebral levels consist- or signs of autonomic dysfunction but impo- ent with an ischaemic lesion (figure). On cor- tence and erectile failure were noted 10 years 1 Bone LJ, Deschênes SM, Balice-Gordon RJ, et al. Connexin 32 and X-linked Charcot-Marie- responding axial cuts, this was shown to before the onset of neurological symptoms. Tooth disease. Neurobiology of Disease involve the region of the anterior horns at He had not taken any medicine which would 1997;4:221–30. cervical level and to prevail on the right half aVect the autonomic nervous system. He did 2 Nicholson G, Corbett A. Slowing of central conduction in X-linked Charcot-Marie-Tooth of the spinal cord at dorsal level. MRI of the not have a habit of drinking. neuropathy shown by brain stem auditory cerebellum and brain stem was normal. Cer- Physical examination on admission de- evoked responses. J Neurol Neurosurg Psychiatry ebral angiography showed an irregular steno- tected no signs of anaemia, heart failure, or 1996; 61:43–6. sis of the right and left cervical vertebral dehydration. Neurological examination 3 Paulson H, Deschênes S, Scherer S, et al. CNS white matter abnormalities in a patient with artery typical of a dissection. The patient was showed dysaesthesia and decreased sensation X-linked Charcot-Marie-Tooth disease treated with oral anticoagulants. One year of all modalities in distal parts of all the limbs. (CMTX). Am J Hum Genet 1994;55:497. later, the sequelae were a spastic paraparesia Deep tendon reflex was absent in the lower 4 Latour P, Fabreguette A, Ressot C, et al.New mutations in the X-linked form of Charcot- with right sided central pain and mild urinary limbs, and Babinski’s sign was positive Marie-Tooth disease. Eur Neurol 1997;37:38– retention. MRI and MRA showed the resolu- bilaterally. Mild limb ataxia was seen in the 42. tion of the cord signal and normal right and four limbs, and Romberg’s test was positive. 5 Bell C, Willison H, Clark C, et al. CNS left vertebral artery. Haematological studies disclosed mild abnormalities in a family with a connexin 32 mutation and peripheral neuropathy. Eur J The cervical cord is mainly supplied by macrocytic hyperchromic anaemia (haemo- Hum Genet 1996;4(suppl 1):136 radicular arteries rising from the vertebral globin 14.0 g/dl, mean corpuscular volume 6 Garcia CA, Malamut RE, England JD, et al. artery. Thus,vertebral artery dissection can 104 fl, mean corpuscular haemoglobin con- Clinical variablility in two pairs of identical twins with Charcot-Marie-Tooth disease type lead to an ischaemia limited to the cervical centration 35.2 pg), with a few (3%) 1A duplication. Neurology 1995;45:2090–3. cord. Extensive ischaemia to the dorsal cord hypersegmented polymorphonuclear cells. (T5) is uncommon. Our results suggest that His serum vitamin B12 concentration was this area is sometimes supplied from the ver- markedly decreased (38 pg/ml; normal 249– Isolated ischaemia of the spinal cord tebral artery. Some authors state that this 938 pg/ml). Intrinsic factor and parietal cell due to bilateral vertebral artery region could be a critical zone and its vascu- antibodies were positive in the serum. Echo dissection larisation could be provided from the arterial cardiography showed no evidence of heart cervical cord region.5 The bilateral ischaemic failure. In a study of peripheral nerve Clinical features in vertebral artery dissection lesions extending through several cervical conduction, amplitudes of sensory nerve are rarely associated with an ischaemic lesion and dorsal segments are in favour of water- action potentials were slightly decreased in of the spinal cord.1 The few cases related and shed infarcts caused by hypoperfusion due to the lower limbs. The somatosensory evoked studied with MRI strictly involve the cervical bilateral vertebral artery dissection. potential on median nerve stimulation cord.2–4 We add another patient with sponta- showed a moderately prolonged central con- P GARNIER neous bilateral vertebral artery dissection in D MICHEL duction time. Urodynamic studies disclosed whom the particularity was an isolated exten- R PEYRON uninhibited neurogenic bladder with detru- sive ischaemia of the spinal cord from C4 to O BEAUCHET sor sphincter dyssynergia. T5 vertebral levels. Department of Neurology Results of the autonomic nervous system A previously healthy 45 year old woman F LE BRAS tests before and 6 months after treatment are had paresthesiae of the right ankle lasting a F G BARRAL given in the table. When the patient was tilted few days. Ten days later, she had a right sided Department of Neuroradiology, University Hospital up to 60 degrees, he experienced dizziness scapulothoracic pain and suddenly developed Saint-Etienne, 42055 Saint -Etienne, France and a significant fall in systolic blood pressure Letters, Correspondence, Book reviews 805 over 30 mm Hg with normal heart rate nal cord induce the dysfunction of postgan- response. His serum noradrenalin concentra- glionic fibres by a trans-synaptic eVect.78 tion was reduced at rest, and its increase after Vitamin B12 is related to the methylation CORRESPONDENCE tilting up was minimal. Sudomotor function reaction regulated by S-adenosylhomocystine was evaluated by sympathetic skin response and S-adenosylmethionine.9 This reaction 3 (SSR) and local sweat response to acetylcho- has a crucial role in the myelin formation 4 line (Ach). associated with neurological deficits in pa- Before treatment, the SSR amplitude was tients with vitamin B12 deficiency. Dysfunc- Sandifer’s syndrome and gastro- decreased, and the number and area of sweat tion in unmyelinated sympathetic neurons, oesophageal reflux disease droplets were decreased in responses to however, has not been shown. Our findings intradermal ACh injection. suggest that vitamin B12 is required for the Perkin and Murray-Lyon’s Neurology and the The myelinated fibre density of biopsied gastrointestinal system reviews gastrointestinal 2 physiological function of sympathetic post- sural nerve was 5927/mm . Some thin myeli- 1 ganglionic fibres. disorders with neurological features. The nated fibres were present, as were a few authors do not mention Sandifer’s syndrome, a myelin ovoids. Examination of the teased SHUTA TORU disorder of the upper gastrointestinal tract fibres showed evidence of demyelination TAKANORI YOKOTA with neurological manifestations occurring in (about 20%) and axonal degeneration (about AKIRA INABA children and adolescents. Sandifer’s syndrome 10%). Electron microscopy showed a normal MASANAGA YAMAWAKI is the association of gastro-oesophageal reflux unmyelinated fibre density (30 945 /mm2). MASAHITO YAMADA disease with spastic torticollis and dystonic Collagen pockets (15 000 /mm2), and dener- HIDEHIRO MIZUSAWA body movements. Nodding and rotation of the vated Schwann cell subunits (12 000 /mm2) Department of Neurology, Tokyo Medical and Dental head, neck extension, gurgling sounds, writh- University, Tokyo, Japan were present, but their densities were within ing movements of the limbs, and severe hypo- the normal range for his age.5 MICHIYUKI HAYASHI tonia have been reported.2–4 It is hypothesised A highly sensitive acetylcholinesterase Department of Neurology, Tokyo Metropolitan that such positionings provide relief from (AChE) histochemical test (modified Tago’s Neurological Hospital, Tokyo Japan discomfort caused by acid reflux.2 A causal 6 method) of the sural nerve detected a slightly Correspondence to: Dr T Yokota, Department of relation between gastro-oesophageal reflux reduced density of sudomotor sympathetic Neurology, Tokyo Medical and Dental University, disease and the neurological manifestations of unmyelinated fibres (3500 /mm2; normal 1-5-45 Yoshima, Bunkyo-Ku, Tokyo 113-8519, Sandifer’s syndrome is supported by the reso- 3700–6500 /mm2). Japan. Fax 0081-3-5803-0169. lution of the manifestations on successful Daily intramuscularly administered 1 mg treatment of gastro-oesophageal reflux dis- vitamin B12 for a week then 1 mg once a ease.2–7 The clinical manifestations almost month increased its serum concentration 1 Kalbfleish JM, Woods AH. Orthostatic hypoten- invariably arouse the suspicion of neurological rapidly to normal, resulting in the gradual sion associated with pernicious anemia: report of a case with complete recovery following vita- disease and lead to unnecessary investigative 4 amelioration of orthostatic dizziness, and his min B12 therapy. JAMA 1962;182:198–200. procedures. The intermittent occurrence of neurological symptoms except for erectile 2 Eisenhofer G, Lambie DG, Johnson RH, et al. torticollis with alternating directions, normal failure, after a month. Deficient catecholamine release as the basis of sternocleidomastoid muscles, and normal cer- The abnormalities seen in the autonomic orthostatic hypotension in pernicious anemia. J vical radiographic findings make Sandifer’s nervous system tests also disappeared when Neurol Neurosurg Psychiatry 1982;45:1053–5. 3 Yokota T, Matunaga T, Okiyama R, et al. syndrome a probable diagnosis and necessitate vitamin B12 was given for 6 months (table). Sympathetic skin response in patients with upper gastrointestinal studies.6 The lesion of the baroreflex responsible for multiple sclerosis compared with spinal cord Most patients have no other abnormalities. his orthostatic hypotension is considered to transection and normal control. Brain 1991; Sandifer’s syndrome is manifested by a be in the eVerent pathway because of the pre- 114:1381–94. relatively large number of patients with brain served heart rate response in head up tilt test. 4 Kennedy WR, Sakuta M, Sutherland D, et al. Quantification of the sweating deficiency in damage or metabolic disorders and is often The low serum noradrenalin concentration in diabetes mellitus. Ann Neurol 1984;15:482–8. interpreted as a feature of their basic dis- particular can be explained by disturbance of 5 Kanda T, Tsukagoshi H, Oda M, et al. Morpho- order.4 A high prevalence of Sandifer’s the sympathetic postganglionic fibres. These logical changes in unmyelinated nerve fibers in syndrome was reported in the Brachman-de findings are supported by the decreased SSR the sural nerve with age. Brain 1991;114:585– Lange syndrome.7 These findings may simply amplitude and the reduced local sweat 96. 6 Hayashi M, Yokota T, Miyamoto K, et al. reflect the high prevalence of gastro- response to ACh. By contrast, the density of Acetylcholinesterase histochemistry by Tago’s oesophageal reflux disease among brain dam- the unmyelinated fibres and AchE positive method in human sural nerves. Autonomic aged children rather than a primary feature of fibres were relatively well preserved when his Nervous System (Tokyo) 1990;27:459–64. these disorders.8 7 Cohen J, Low P, Fealy R, . Somatic and age was considered. Furthermore, there was et al Early recognition and treatment of gastro- the rapid recovery of serum noradrenalin autonomic function in progressive autonomic failure and multiple system atrophy. Ann Neurol oesophageal reflux disease in patients with concentraton, the SSR size, and the sweat 1987;22:692–9 Sandifer’s syndrome enhances the success of response to ACh after giving the vitamin B12 8 Mathias CJ, Christensen NJ, Corbeett JL, et al. medical management, is curative for patients supplement. These results suggest dysfunc- Plasma cathecolamine during paroxysmal neu- with no other disorders, and contributes to tion of the sympathetic postganglionic fibres rogenic hypertension in quadriplegic man. Circ Res 1976;39:204–8. improved quality of life for patients with brain 468 without marked morphological change, al- 9 Metz J. Cobalamin deficiency and the pathogen- damage. though we cannot exclude the possibility that esis of nervous system disease. Annu Rev Nutr sympathetic neurons in the brainstem or spi- 1992;12:59–79. DEMETRIOS S THEODOROPOULOS RICHARD F LOCKEY Results of autonomic nervous system tests before and after vitamin B12 treatment Division of Allergy and Immunology H WORTH BOYCE, JR Age matched Before After normal Center for Swallowing Disorders, Department of treatment treatment control Internal Medicine, University of South Florida College of Medicine, and James A Haley Veterans Hospital, Head-up tilting test 13000 Bruce B Downs Boulevard, Tampa,Florida Systolic blood pressure (mm Hg) Supine 104 106 112 - 135 33612, USA 5 min after tilting 71 93 118 - 140 Correspondence to: Dr DS Theodoropoulos, Divi- 15 min after tilting 76 106 sion of Allergy and Immunology, Department of Heart rate (/min) Supine 58 66 59 - 83 Internal Medicine, University of South Florida 5 min after tilting 70 73 65 - 95 College of Medicine and James A. Haley Veterans 15 min after tilting 73 76 Hospital (111D), 13000 Bruce B. Downs Boul- Noradrenaline (pg/ml) Supine 94 177 128 - 512 evard, Tampa, FL 33612, USA. 5 min after tilting 129 286 258 - 752 Sympathetic skin response Amplitude (mV) L palm 0.33 1.9 1.2 - 15.3 1 Perkin GD, Murray-Lyon I. Neurology and the R palm 0.39 1.0 gastrointestinal system. J Neurol Neurosurg Psy- L Sole 0.67 1.9 0.71 - 8.8 chiatry 1998;65:291–300. R Sole 0.61 1.2 2 Kinsbourne M. Hiatus hernia with contortions Local sweat response to acetylcholine of the neck. Lancet 1964;i:1058–61. Number of sweat droplets (/cm2)246942-723 Sutclife J. Torsion spasm and abnormal postures Total area of sweat droplets (mm2/cm2) 0.27 2.86 0.75 - 11.5 in children with hiatus hernia Sandifer’s syndrome. Prog Pediatr Radiol 1969;2:190–7.