European Journal of Neurology 2002, 9: 541–545 LETTERS TO THE EDITOR Hypertensive encephalopathy: persistent MR-abnormalities in a patient with good clinical recovery H. J. J. A. Bernsena, D. J. Venderinkb and J. Meulsteea Departments of aNeurology and bRadiology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands Correspondence: H. J. J. A. Bernsen, Department of Neurology, CanisiusWilhelmina Hospital, Postbus 9015, 6500 GS, Nijmegen, The Netherlands (e-mail: h.bernsen@cwz.nl). Keywords: hypertension, hypertensive encephalopathy, serial magnetic resonance Received 26 November 2001 Accepted 22 May 2002 A common complication of a hypertensive crisis is the development of a hypertensive encephalopathy (HE) resulting from failure of the cerebral autoregulation to maintain the cerebral perfusion pressure within specific upper limits. Usually, one of the first signs of patients with a HE is lethargy, but other neurological deficits such as epileptic seizures and focal neurological signs may also arise. Pathophysiologically, the appearance of oedema because of altered blood brain barrier function is one of the hallmarks of HE. Computed tomography and magnetic resonance imaging (MR imaging) have demonstrated that the formation of oedema is usually restricted to the posterior brain area and the neurological symptoms and MR imaging abnormalities are reported to be completely reversible after adequate treatment (Port and Beauchamp, 1989; Weingarten et al., 1994; Schwartz et al., 1995; Campell and Zimmerman, 1996; Hinchey et al., 1996; Pavlakis et al., 1999; Vaughan and Delanty, 2000). Therefore, the term reversible posterior leukoencephalopathy is frequently used to refer to this syndrome (Hinchey et al., 1996; Pavlakis et al., 1999). In this report, a 48-year-old male patient who developed a hypertensive crisis with a HE is described along with follow-up MR imaging findings, which show only partial resolution of the intracerebral abnormalities. In the days before admission, this patient showed an increased lethargy, memory disturbances and perseveration and complained of a Ó 2002 EFNS Figure 1 (a) Magnetic resonance imaging of the brain a few days after admission; transversal T2-weighted image showing a diffuse hyperintense signal throughout the subcortical areas, not confined to the posterior regions. (b) Transversal T2-weighted images of the brain 5 months later showing only a slight reduction of the hyperintense signal. blurred vision. There was no previous history of hypertension or other diseases. On physical examination the patient appeared disoriented and blood pressure was 185/ 120 mmHg. There were decreased pupillary reflexes with papillary oedema of both eyes. No sensorimotor abnormalities were present, but reflexes were brisk. Plantar reflexes showed an extensor response bilaterally. Hypertension of the patient was treated promptly with sodium nitroprusside with subsequent resolution of the neurological abnormalities. The patient was discharged 3 weeks later. An electroencephalogram performed 1 day after hospital admission showed periodic bilateral triphasic wave activity of 2–5 Hz interrupted by repetitive discharges of triphasic waves with slight predominance over the left hemisphere. Magnetic resonance imaging of the brain 2 days after admission showed a diffuse hyperintense signal throughout the white matter on T2-weighted images, not confined to the posterior region in the brain (Fig. 1a). Although some reduction of the hyperintense signals was observed on subsequent MR images performed 3 and 5 months later, a substantial area of unchanged hyperintense signal in the subcortical region remained present demonstrating that the changes observed after HE on MR imaging only partly disappeared, although our patient showed a good clinical recovery after antihypertensive treatment (Fig. 1b). Therefore, these observations suggest that the term reversible posterior encephalopathy is not always appropriate to describe the clinical and imaging features of HE. References Campell BG, Zimmerman RD (1996). Emergency magnetic resonance of the brain. Topics Magn Reson Imag 9:208–227. Hinchey JH, Chaves C, Appignani B et al. (1996). A reversible posterior leukoencephalopathy syndroma. N Engl J Med 334:494–500. Pavlakis SG, Frank Y, Chusid R (1999). Hypertensive encephalopathy, reversible occipitoparietal encephalopathy: three names for an old syndrome. J Child Neurol 14:277– 281. Port JD, Beauchamp NJ (1989). Reversible intracerebral pathologic entities mediated by vascular autoregulatory dysfunction. Radiographics 18:353–367. Schwartz RB, Bravo SM, Klufas RA et al. (1995). Cyclosporine neurotoxicity and its hypertensive encephalopathy; CT and MR findings in 16 cases. Am J Roentgenol 165:627–631. Vaughan CJ, Delanty N (2000). Hypertensive emergencies. Lancet 359:411–417. Weingarten K, Barbut D, Filippi C, Zimmerman R (1994). Acute hypertensive encephalopathy: findings on spin-echo and gradient-echo MR imaging. Am J Roentgenol 162:665–670. 541 542 Letters to the Editor SSPE – a forgotten disease? a a F. G. Joseph , J. Jacob and D. Carringtonb a Institute of Clinical Neurosciences, Frenchay Hospital, Bristol;bPublic Health Department, St Michael’s Hospital, Southwell Street, Bristol, UK Correspondence: F. G. Joseph, 19 Heol Pantruthin, Pencoed, Mid-Glamorgan, South Wales CF35 5PA, UK (Tel.: 01656 862027; E-mail: fgjoseph@yahoo.co.uk). Keywords: CNS infection, MMR vaccine, SSPE, subacute sclerosing panencephalitis, transverse sinus occlusion, viral infection of CNS Received 8 April 2002 Accepted 30 May 2002 Sir, Subacute sclerosing panencephalitis (SSPE) is a rare and fatal chronic degenerative encephalitis because of a persisting infection of the brain by a defective measles virus. A 20-year-old right-handed female in the last trimester of her second pregnancy was admitted as an emergency with a 10-day history of headache and 4 days of progressive visual loss in the left eye with memory difficulties, abnormal speech and vomiting. She never had measles vaccination and at 1 year of age had an uncomplicated childhood measles infection. Examination revealed that she was confused and poorly cooperative with a nominal dysphasia and mild right hemiparesis, but no meningism or pyrexia. Visual acuity was only to finger counting on the left, with fundoscopic evidence of ischaemia affecting the left papillomacular bundle. Routine serum biochemistry and haematology, inflammatory markers, an auto-immune profile and thrombophilia screen were all normal or negative. Initial magnetic resonance imaging (MRI) brain scan and MR venography showed thrombotic occlusion of the left transverse sinus. Cerebrospinal fluid (CSF) opening pressure was normal, but Severe axonal polyradiculoneuritis and brainstem encephalitis due to Mycoplasma pneumoniae infection A. Harloff, S. Voigt, A. Hetzel, F. X. Glocker and T. Els Department of Neurology and Clinical Neurophysiology, there was a lymphocyte pleocytosis of 25 with a slightly elevated protein of 0.6 g/l, normal CSF-to-serum glucose ratio and positive oligoclonal bands. Methylprednisolone and acyclovir were commenced, to cover the possibilities of a central nervous system (CNS) vasculitis and viral encephalitis, respectively. This was followed by full anticoagulation with low molecular weight heparin. There was progressive right hemiparesis, with homonymous hemianopia and later focal seizures affecting the right hand, which were initially resistant to antiepileptic drugs. Multiple electroencephalographs showed irregular slow activity in keeping with an encephalopathic process but without periodic complexes or definite epileptiform abnormalities. Serial MRI brain scans showed progressive cortical and subcortical high signal abnormalities that initially involved the posterior left hemisphere and later much of the right hemisphere, reflecting relentless neurological decline. CSF viral studies revealed a striking rise in the titre of measles-specific IgG antibodies between samples, with strong evidence for SSPE and intrathecal production of antibodies. Furthermore, there were specific defects in the matrix (M) gene of the virus that is known to be causally associated with SSPE. The measles genotype identified in our patient was genotype D1. The WHO reference strain of genotype D1 is ‘Bristol.UNK/74’, isolated in Bristol in 1974 and although is currently inactive, it was one of the wild types of measles virus in the UK during her childhood in Bristol. Further confirmation of measles encephalitis was obtained directly from brain biopsy that showed viral inclusion bodies, perivascular cuffing with lymphocytes, reactive astrocytosis in the cortex and white matter with some piecemeal necrosis. Prior to her demise and the onset of a persistent vegetative state, a healthy male foetus was delivered by Caesarean section at 34 weeks gestation. The development of bronchopneumonia 3 months after her initial admission, proved to be a terminal event. Subacute sclerosing panencephalitis during pregnancy is rare and has been reported in patients up to 27 years old (Wirguin et al., 1988). The youngest case of SSPE during pregnancy reported hitherto was in a 14-year-old girl in the last trimester of pregnancy who presented with chorioretinitis and progressive dementia (Jayawant et al., 2000). While it is possible that the association of SSPE and pregnancy might have been coincidental, the immunosuppressed state of pregnancy could have led to a more fulminant course (Wirguin et al., 1988). It appears that the transverse sinus thrombosis in this case was indeed a chance finding and unlikely to have accounted for the serious clinical consequences observed. Ocular involvement in SSPE precedes or accompanies other neurological signs in 50% of patients and is attributed to direct viral invasion of the retina (Caruso et al., 2000). The current controversy over the safety of the MMR vaccine and the consequent fall in immunization rate for this disease gives cause for concern about the resurgence of SSPE in the long term. The public perception of the benign outcome of measles infection in childhood should be tempered by greater awareness of the real and quantifiable risk of severe longterm measles complications in adulthood. References Caruso J, Robbins-Tien D, Brown W, Antony J, Gascon G (2000). Atypical chorioretinitis as an early presentation of subacute sclerosing panencephalitis. J Paediatr Ophthalmol Strabismus 37:119–122. Jayawant S, Fey-Waboso A, Wallace S et al. (2000). Retinitis and dementia in a pregnant girl: an unusual case. Eur J Paediatr Neurol 4:177–179. Wirguin I, Steiner I, Kidron D et al. (1988). Fulminant subacute sclerosing panencephalitis in association with pregnancy. Arch Neurol 45:1324–1325. University of Freiburg, Freiburg, Germany (fax: 49-761-270-5390; e-mail: els@nz11.ukl.uni-freiburg.de). Correspondence: Dr Thomas Els, Department of Neurology and Clinical Neurophysiology, University of Freiburg, Breisacher Str. 64, D-79106 Freiburg, Germany Keywords: axonal polyradiculoneuritis, brainstem encephalitis, Mycoplasma pneumoniae, western blot Received 17 December 2001 Accepted 7 June 2002 Ó 2002 EFNS European Journal of Neurology 9, 541–545 Letters to the Editor Mycoplasma pneumoniae (Mp) is a typical respiratory tract pathogen in children and young adults that may affect other organs (Lehtokoski-Lehtiniemi and Koskiniemi, 1989; Thomas et al., 1993). Immunemediated mechanisms (Biberfeld, 1971), direct invasion of the central nervous system (CNS) (Abramovitz et al., 1987) or the existence of a neurotoxin (Thomas et al., 1996) are proposed pathomechanisms of extrapulmonary complications. We are reporting on a healthy 22-yearold woman who developed acute progressive neurological symptoms, with disturbance of consciousness, bilateral facial paresis, ptosis, dysphagia and paresis of the soft palate 5 days after an unspecific respiratory tract infection. Motor testing showed a floppy tetraparesis and generalized areflexia without pathological reflexes. Sensation was normal. Intubation and artificial ventilation became necessary because of progressive impairment of vigilance and increasing respiratory failure. Clinical examination results of her skin, cardiovascular, pulmonary and gastrointestinal systems were normal. On admission, cerebrospinal fluid (CSF) revealed: 97 cells/ll (<5/ll), total protein 610 mg/l (<450 mg/l), glucose 51 mg/dl (45–75 mg/dl). Two weeks later CSF showed 12 cells/ll (80% lympho-, 20% monocytes), total protein 5.733 mg/l. Initial blood values showed slightly elevated: C-reactive protein 4.4 mg/dl (0–0.5 mg/dl) and 15 400 leucocytes/ll (4.3–10 000/ll). All other routine blood values were normal. Mycoplasma IgG titres by complement fixation titre increased from 1 : 20 on admission to 1 : 80 at control 1 week later. Western blot of serum probe detected IgA, IgG bands and Mp-specific proteins P 100 and P 65. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) for Mp were negative in subsequent CSF samples. Cold agglutinins and Coombs test were negative. There was no evidence of other infectious agents in broad blood and CSF screening with cultures, ELISA and PCR. There were no signs of antineuronal antibodies, collagenosis or vasculitis. Motor nerve conduction studies showed absent F-waves. Electromyography revealed excessive spontaneous activity in distal and proximal muscles, suggesting severe axonal damage. Median nerve somatosensory-evoked potentials showed transient abnormalities consistent with central afferent dysfunction. Magnetic resonance imaging (MRI) of the brain was normal. MRI of the spinal cord (Fig. 1) showed changes compatible with polyradiculoneuritis. Under the suspicion of acute encephalitis combined with a Guillain–Barré-like syndrome (GBS), the patient immediately received ceftriaxone, ampicillin and aciclovir, with additional doxycycline on positive results for Mp. Intravenous immunoglobulin therapy (0.4 g/kg bw/ day) was performed twice. On transfer to the rehabilitation clinic, the patient was alert and breathing autonomously by tracheostoma. Communication was possible by eye movements. Facial nerves were paretic, gag and cough reflexes were absent. The patient could open her mouth, stick her tongue out and move her head. Tetraplegia and areflexia persisted. Eighteen months later, she still showed slight psychomotor delay without other neuropsychological deficits. Because 543 of moderate distally accentuated tetraparesis, she was unable to walk unsupported. The upper respiratory tract infection in this patient followed by CNS manifestations 1 week later is typical of Mp-associated complications. Western blot, the fourfold rise of antibody titre and exclusion of typical differential diagnosis proved acute Mp infection. GBS is preceded by this agent in 5% (Goldschmidt et al., 1980). However, the severe axonal polyradiculoneuropathy found here is rare (Feasby et al., 1986). Furthermore, GBS is not accompanied by fever, acute inflammation reaction or initial pleocytosis greater than 50 cells/ll in CSF (Asbury and Cornblath, 1990). We therefore, consider a rare association of Mp-infection with brainstem encephalitis manifesting with somnolence, agitation, the necessity of ventilation, initial CSF pleocytosis of 97 cells/ll and transient central changes in median nerve somatory evoked potentials. Pleocytosis in CSF and neurological symptoms should always be taken into account following a febrile respiratory tract infection with Mp in young patients. References Figure 1 Sagittal T1-weighted MRT of the spinal cord showing pathological contrast enhancement of the conus, epiconus and cauda equina. Ó 2002 EFNS European Journal of Neurology 9, 541–545 Abramovitz P, Schvartzman P, Harel D, Lis I, Naot Y (1987). Direct invasion of the central nervous system by Mycoplasma pneumoniae: a report of two cases. J Infect Dis 155:482–487. Asbury AK, Cornblath DR (1990). Assessment of current diagnostic criteria for Guillain– Barré syndrome. Ann Neurol 27:21–24. Biberfeld G (1971). Antibodies to brain and other tissues in cases of Mycoplasma pneumoniae infection. Clin Exp Immunol 8:319–333. Feasby TE, Gilbert JJ, Brown WF et al. (1986). An acute axonal form of Guillain–Barré polyneuropathy. Brain 109:1115–1126. Goldschmidt B, Menonna J, Fortunato J, Dowling P, Cook S (1980). Mycoplasma antibody in Guillain–Barré syndrome and other neurological disorders. Ann Neurol 7:108–112. Lehtokoski-Lehtiniemi E, Koskiniemi ML (1989). Mycoplasma pneumoniae encephalitis: a severe entity in children. Pediatr Infect Dis J 8:651–653. Thomas L, Aleu F, Bitensky MW, Davidson M, Gesner B (1996). Studies of PPLO infection. The neurotoxin of Mycoplasma neurolyticum. J Exp Med 124:1067–1082. Thomas NH, Collins JE, Robb SA, Robinson RO (1993). Mycoplasma pneumoniae infection and neurological disease. Arch Dis Child 69:573–576. 544 Letters to the Editor Cerebellar ataxia after repeated hypoglycemia M. Schwaninger, S. Haehnel, K. Hess, B. Fohr, P. Nawroth and W. Hacke Departments of Neurology and Internal Medicine, University of Heidelberg, Heidelberg, Germany Correspondence: Markus Schwaninger, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany (fax: 49-6221565461; e-mail: markus.schwaninger@ med.uni-heidelberg.de) Keywords: ataxia, hypoglycemia, myelinolysis Received 8 April 2002 Accepted 12 June 2002 Dear Sir, The brain depends on glucose as an energy substrate. However, the vulnerability of brain areas toward hypoglycemia varies. Cortical neurons are especially sensitive leading to cognitive deficits after hypoglycemia. Here we present the case history of a patient with prolonged cerebellar ataxia. A 41-year-old male patient presented with a 2-year history of severe hypoglycemia with dizzy spells and tonic clonic seizures. In addition, profound memory deficits and a gait disorder had slowly developed over 6 months. At neurological examination he had normal eye movements without nystagmus and no dysmetria of the extremities, but showed a severe gait ataxia that prohibited standing or walking without support. He had a mild action tremor of both arms. Furthermore, there was a symmetric distal weakness of the arms and legs. Tendon reflexes apart from the ankle reflex were preserved. Sensation of all qualities, including vibration, was completely normal. Electrophysiological tests confirmed an axonal motoric neuropathy, while the sensory conduction velocity of the sural nerve and the somatic-evoked potentials were marginally decreased or normal. Neuropsychological testing disclosed deficits of memory and a a visuoconstructional apraxia. Positron emission tomography showed a normal distribution of [18F]fluorodeoxyglucose in the brain. However, T2-weighted magnetic resonance (MR) images revealed symmetric hyperintensities in the middle cerebellar peduncles (Fig. 1 (left)) and in the dorsal limbs of the capsula interna (Fig. 1 (right)). Figure 1 T2-weighted MR image (TR ¼ 3000 ms; TE ¼ 60 ms; slice thickness ¼ 4 mm) showing hyperintensities in both middle cerebellar peduncles (left) and in the dorsal limbs of the capsula interna (right). After resection of a pancreatic insulinoma, serum glucose concentrations normalized. At follow-up 4 months after surgery the gait ataxia had partially improved. He was then able to walk without support. The MR lesions in the middle cerebellar peduncles and in the dorsal limbs of the capsula interna, however, were still apparent on MRI. In sum, our patient suffered from cognitive impairment and a predominantly motoric neuropathy, both well-known sequelae of severe hypoglycemia (Heckmann et al., 2000). In addition, he had a cerebellar gait ataxia. In contrast to global ischemic or hypoxic brain damage, in hypoglycemia cerebellar Purkinje cells are usually preserved (Auer and Siesjö, 1993). The resistance of the cerebellar cortex toward hypoglycemia has been attributed to an efficient glucose uptake in the cerebellum (LaManna and Harik, 1985; Kim et al., 2000). Nevertheless, hypoglycemic patients suffer occasionally from gait ataxia (Esforzado et al., 1993; Rajbhandari et al., 1998; Kim et al., 2000). In two of the patients reported in the literature with cerebellar ataxia after hypoglycemia, MRI suggested a pontine myelinolysis that was attributed to the preceding hypoglycemia (Esforzado et al., 1993; Rajbhandari et al., 1998). In our patient MRI showed lesions with a prolongation of T2 relaxation time in the middle cerebellar peduncle and in the dorsal limbs of the capsula interna, a common location of extrapontine myelinolysis (Bekiesinska-Figatowska et al., 2001). Hypoglycemia might have induced an extrapontine myelinolysis, which has already been associated with cerebellar ataxia (Defebvre et al., 1995). This and the other cases in the literature illustrate that the range of neurologic sequelae of hypoglycemia includes ataxia. Hypoglycemia should be considered in the differential diagnosis of ataxia of acute onset. References Auer RN, Siesjö BK (1993). Hypoglycaemia: brain neurochemistry and neuropathology. Baillieres Clin Endocrinol Metab 7:611– 625. Bekiesinska-Figatowska M, Bulski T, Rozyczka I, Furmanek M, Walecki J (2001). MR imaging of seven presumed cases of central pontine and extrapontine myelinolysis. Acta Neurobiol Exp (Warsz) 61:141–144. Defebvre L, Rogelet P, Destee A, Verier A (1995). Regressive dystonia and cerebellar ataxia: two unusual symptoms in central pontine myelinolysis. J Neurol 242:450–454. Esforzado N, Poch E, Cases A, Cardenal C, Lopez-Pedret J, Revert L (1993). Central pontine myelinolysis secondary to frequent and rapid shifts in plasma glucose in diabetic haemodialysis patient. Nephrol Dialysis Transplantation 8:644–646. Heckmann JG, Dietrich W, Hohenberger W, Klein P, Hanke B, Neundörfer B (2000). Hypoglycemic sensorimotor polyneuropathy Ó 2002 EFNS European Journal of Neurology 9, 541–545 Letters to the Editor 545 associated with insulinoma. Muscle Nerve 23:1891–1894. Kim DE, Park SH, Kim SK et al. (2000). Hypoglycemia-induced cerebellar dysfunction and quantitative positron emission tomography study. Neurology 55:418–422. LaManna JC, Harik SI (1985). Regional comparison of brain glucose influx. Brain Res 326:299–305. Rajbhandari SM, Powell T, Davies-Jones GA, Ward JD (1998). Central pontine myelinolysis and ataxia: an unusual manifestation of hypoglycaemia. Diabet Med 15:259–261. Broad therapeutic benefits in patients with probable vascular dementia or Alzheimer’s disease with cerebrovascular disease after treatment with galantamine beneficial to patients with AD + CVD and VaD. Galantamine, a reversible, competitive AChEI and a positive allosteric modulator of nAChRs (Samochocki et al., 2000), may optimize cholinergic neurotransmission, thus producing clinically important benefits in the symptomatic treatment of patients with dementia related to CVD. Benefits in AD have been demonstrated. The recent multicentre, double-blind, 6-month international trial with galantamine (Erkinjuntti et al., 2002) was the first randomized, placebo-controlled study showing clinically relevant benefits with a cholinergic drug in patients with AD + CVD or probable VaD. A total of 592 patients (457 completed the study) fulfilled NINCDS–ADRDA or NINDS– AIREN criteria and were randomly assigned to receive either galantamine 24 mg/day or placebo. The high sensitivity and specificity of these criteria distinguish AD with CVD from probable VaD more accurately than diagnostic/imaging methods. AD + CVD was diagnosed in 48 and 50% of patients in the galantamine and placebo groups, respectively, with probable VaD present in 43 and 41% of patients, respectively. After 6 months, galantamine produced a broad range of significant benefits. Cognition (using the ADAS-cog/11 – a more sensitive instrument than the MMSE) significantly improved versus placebo and baseline in the overall analysis and in subgroup analyses of patients with probable VaD or AD + CVD. Using the CIBIC-plus to measure overall clinical response to therapy, significantly more galantamine-treated patients remained stable or improved compared with placebo-treated patients. Galantamine also demonstrated significant benefits on patients’ activities of daily living (DAD) and behavioural symptoms (NPI) compared with placebo-treated patients. During a 6-month open-label extension of this trial, all patients received galantamine 24 mg/day. Preliminary results indicate sustained cognitive benefits at 12 months, with patients receiving galantamine in both phases maintaining cogni- tion at or above baseline levels for the entire study period (Bullock and Lilienfeld, 2001). Although little published data show clinically relevant benefits with preventive treatments for VaD, these results offer encouraging evidence of important treatment effects in both VaD and AD + CVD, most notably maintenance of cognitive function for at least 6 months. T. Erkinjuntti Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland Correspondence: Timo Erkinjuntti, Department of Clinical Neurosciences, Helsinki University Central Hospital, PO Box 300, 00029 HYKS, Finland (e-mail: timo.erkinjuntti@hus.fi). Keywords: Alzheimer’s disease, cerebrovascular disease, cognition, galantamine, global function, vascular dementia Received 30 May 2002 Accepted 5 June 2002 Sir, Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common causes of dementia among elderly persons (Evans et al., 1989; Rockwood et al., 2000), together accounting for nearly twothirds of all cases. The considerable overlap between AD and VaD – progressive cognitive, functional and behavioural decline, pathologic brain changes, associated risk factors and neurochemical deficits (Kalaria and Ballard, 1999; Erkinjuntti, 2001) – have led to underrecognition of AD with cerebrovascular disease (AD + CVD), where features of both AD and VaD coincide. Several studies (Mendez et al., 1999; Kumar et al., 2000; Moretti et al., 2001) demonstrate the beneficial effects of donepezil and rivastigmine in the treatment of VaD; however, small patient populations and lack of diagnostic/imaging techniques that can adequately distinguish patients with AD + CVD and VaD lead to questions regarding the impact of these drugs in these populations. In response to the letter by Moretti and colleagues regarding their 16-patient study of rivastigmine versus cardioaspirin in probable VaD, we provide even stronger evidence that galantamine is Ó 2002 EFNS European Journal of Neurology 9, 541–545 References Erkinjuntti T (2001). Clinical deficits of Alzheimer’s disease with cerebrovascular disease and probable VaD. Int J Clin Pract (Suppl) May 120:14–23. Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV (2002). Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial. Lancet 359:1283–1290. Evans DA, Funkenstein HH, Albert MS et al. (1989). Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA 262:2551–2556. Kalaria RN, Ballard C (1999). Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 13:S115–S123. Kumar V, Anand R, Messina J, Hartman R, Veach J (2000). An efficacy and safety analysis of Exelon in Alzheimer’s disease patients with concurrent vascular risk factors. Eur J Neurol 7:S159–S169. Mendez MF, Younesi FL, Perryman KM (1999). Use of Donepezil for vascular dementia: preliminary clinical experience. J Neuropsychi Clin Neurosci 11:268–270. Moretti R, Torre P, Antonello RM, Cazzato G (2001). Rivastigmine in subcortical vascular dementia: a comparison trial on efficacy and tolerability for 12 months. Eur J Neurol 8:361–362. Rockwood K, Wentzel C, Hachinski V, Hogan DB, MacKnight C, McDowell I (2000). Prevalence and outcomes of vascular cognitive impairment. Vascular cognitive impairment investigators of the Canadian Study of Health and Aging. Neurology 54:447–451. Samochocki M, Zerlin M, Jostock R et al. (2000). Galantamine is an allosterically potentiating ligand of the human alpha4/ beta2 nAChR. Acta Neurologica Scand 176 (Suppl.):68–73.