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Movement disorders as presenting symptoms of AIDS
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Case report
Movement disorders as presenting symptoms of AIDS Marcello Moccia a, Marina Picillo a, Antonio Carotenuto a, Francesco Barbato a, Ivan Gentile b, Giuseppe Orefice a,* a b
Department of Neurosciences, University of Naples ‘‘Federico II’’, via Sergio Pansini 5, 80131 Napoli, Italy Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples ‘‘Federico II’’, via Sergio Pansini 5, 80131 Napoli, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 March 2013 Received in revised form 3 April 2013 Accepted 4 April 2013
Opportunistic infections are frequently reported to induce movement disorders in late stages of HIV. We report a case of a 32-year-old woman who presented headache and fever that was resistant to antipyretic drugs and to common antibiotics. Hereafter her right limbs were affected by several hyperkinetic movement disorders (ballismus, chorea, dystonia, athetosis). Brain MRI showed a mass lesion involving left basal ganglia. Serological tests were positive for HIV and for Toxoplasma gondii. Clinical features, therapeutical approaches, prognostic factors and possible pathogenesis are discussed. A literature review of cases of movement disorders associated with AIDS is provided. ß 2013 Elsevier GmbH. All rights reserved.
Keywords: HIV Toxoplasma gondii Movement disorders Chorea Ballismus AIDS
Introduction Movement disorders are frequently reported as a possible complication of Human Immunodeficiency Virus infection (HIV) and can rarely represent its initial manifestation [1]. Hemichorea (HC) is one of the most recurring HIV-related movement disorders, and is usually caused by basal ganglia lesions. Cerebral toxoplasmosis is a common opportunistic infection in Acquired Immune Deficiency Syndrome (AIDS) and its basal ganglia involvement may be complicated by a subacute onset of HC [2–4]. However HIVrelated movement disorders have several unsettled issues such as therapeutical approaches, prognostic factors and pathogenesis. Case report A 32-year-old women was admitted at our Department after one week from the onset of bilateral pulsating headache and fever (almost 101 8F) that seemed to be resistant to antipyretic drugs and to common antibiotics. In addition to this she complained of a subacute onset of hyperkinetic movement disorders in her right limbs (Video 1). The hyperkinetic movements affected proximal
Abbreviations: HIV, Human Immunodeficiency Virus infection; HC, Hemichorea; AIDS, Acquired Immune Deficiency Syndrome; HAART, Highly Active AntiRetroviral Therapy. * Corresponding author. Tel.: +39 081 746 2670; fax: +39 081 746 4348. E-mail address: orefi[email protected] (G. Orefice).
and distal muscles of the extremities and ranged from ballistic to choreic or athetotic movements with occasional dystonic jerks. No further signs were found at neurological examination. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.baga.2013.04.004. Brain MRI showed a mass lesion extending from left caudate to midbrain, with marked central necrotic component as for abscessual collection. The lesion presented a ring-enhancement after gadolinium administration. This lesion provoked third ventricle and midbrain dislocation with slight signs of transtentorial herniation. Serological tests were positive for HIV. The patient underwent further evaluations to assess the HIV state, in particular quantitative HIV-RNA assay (70,000 copies/mL) and CD4+ T lymphocytic subpopulation count (250 cells/mL) were performed. Highly Active Anti-Retroviral Therapy (HAART) was started with Tenofovir Disoproxil (245 mg/day) and Lopinavir/Ritonavir (400/100 mg/ day). Furthermore serological tests were positive for Toxoplasma gondii (T. gondii IgG 25 UI/mL with 1–4 as normal value; T. gondii IgM 0.01 UI/mL with <0.65 as normal value). A presumptive diagnosis of HIV-related cerebral Toxoplasmosis was performed and therapy was improved by adding Pyrimethamine (50 mg/day), Sulphadiazine (4 g/day), Desametazone (12 mg/day) and Glicerole (100 mg/day) to control both Toxoplasmosis infection and cerebral oedema. Moreover Haloperidol (3 mg/day) was prescribed for the hyperkinetic movement disorders. At 1 month follow-up brain MRI showed a reduction in size and enhancement of the lesion. Hyperkinetic movement disorders
2210-5336/$ – see front matter ß 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.baga.2013.04.004
Please cite this article in press as: Moccia M, et al. Movement disorders as presenting symptoms of AIDS. Basal Ganglia (2013), http:// dx.doi.org/10.1016/j.baga.2013.04.004
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BAGA-97; No. of Pages 4 M. Moccia et al. / Basal Ganglia xxx (2013) xxx–xxx
2
Table 1 Movement disorders with clear aetiology in adult HIV patients.
Athetosis
Chorea
Sex/age
Onset. Additional symptoms
Aetiology [Reference]
Neuroimaging
Years of AIDS
Treatment
Course
M/55
S. Dysphasia
H. Zoster [5]
0
Acyclovir, Tetrabenazine
Partial recovery
F/33
S. n.r.
JC virus [5]
3
Cytosine arabinoside
Death
F/28
S. Headache, fever, weakness
T. gondii [5]
T2 multiple hyperintense lesions (internal capsule, left lentiform and subthalamic nuclei) T2 multiple hyperintense lesions Multiple CT hypodense lesions of thalami and lentiform nuclei
3
Pyrimethamine, Sulphadiazine
Death
M/28
S. Diarrhoea
Cryptococcus spp [12]
1
Fluconazole, Itraconazole
F/49
S. Behavioural abnormalities, dementia S. Behavioural abnormalities S. Dementia
HIV encephalitis [10]
Hypodense CT lesion of right subthalamus Cortical atrophy
0
n.d.
Partial recovery Death
Normal
2
T2 multiple hyperintense lesions (white matter, internal capsules) T2 multiple hyperintense lesions (pons, mesencephalon, internal capsule) T2 hyperintense lesion of subthalamic nucleus T2 multiple hyperintense lesions (mesencephalon, basal ganglia, thalamus, internal capsule, frontal operculum) T2 hyperintense lesion of capsule-talamic nuclei T2 hyperintense lesion of right cerebral peduncle, right frontal lobe, temporo-occipital area Normal
6
HAART (from 1 year), withdrawal of Interferon HAART
Complete recovery Complete recovery
1
n.d.
Death
1
HAART (from 1 year), Pyrimethamine, Sulphadiazine Phenobarbital, Fluconazole, Clindamycin
Complete recovery Death
0
TrimethoprimSulfamethoxazole Pyrimethamine, Sulphadiazine
Complete recovery Partial recovery
5
Withdrawal of Pentamidine
Complete recovery
0
Penicillin
n.r.
n.r.
Partial recovery Progressive course
0
HAART, Tetrabenazine
4
HAART, Acyclovir, Methylprednisolone
M/50 M/49
Drug-induced (Interferon) [11] HIV encephalopathy [2] JC virus [2]
M/27
A. Ataxia, weakness, impaired distal touch and pain sensitivity A. Fever
M/25
S. Fever
T. gondii [2]
F/59
T. gondii [3]
M/26
S. Headache, nausea, vomit, fever S. Seizures
F/28
A. n.r.
M/35 F/32
C. Ataxia, apraxia, dysarthria C. Dementia
M/47
C. Dementia
M/24
S. Behavioural abnormalities, confusion
Dyskinesias
M/36
A. Headache, fever, dysarthria
S. Pneumoniae [2]
Diffuse cerebral oedema
4
Ampicillin, Chloramphenicol
Death
Parkinsonism
M/65
C. Dementia
Cerebral atrophy
0
HAART, Levo-Dopa
M/49
S. Confusion
HIV encephalopathy [21] T. gondii [13]
0
M/31
S. Behavioural abnormalities C. Fever, asthenia, anorexia, weight loss
T2 hyperintense lesion of right lenticular nucleus Hypointense signal of left lenticular nucleus Hypodense CT lesion of left internal capsule, left external capsule and lower portion of lenticular nuclei T2 multiple hyperintense lesions Cortical atrophy, T2 multiple hyperintense lesions of frontal white matter T2 multiple hyperintense lesions of subcortical white matter Normal
HAART, Pyrimethamine, Clindamycin Ethambutol, Pyrazinamide
Partial recovery Partial recovery Progressive course Complete recovery
M/57
M/49
T. gondii [2]
T. gondii [4]
Metabolic (Pentamidine-induced Hypoglycaemia) [5] T. pallidum [6] HIV encephalopathy [7] HIV encephalopathy [8] HIV encephalitis [9]
M. tubercolosis [14] M. tubercolosis [15]
M/50
C. n.r.
M/63
S. Dementia
M/37
S. n.r.
HIV encephalopathy [18]
M/35
S. Tourette-like tics
M/63
C. Weight loss
Drug-induced (Risperidone) [19] Cryptococcus spp [20]
M/38
S. Nausea, vomit
M/29
S. Hypomania, anxiety
HIV encephalopathy [16] HIV encephalopathy [17]
Drug-induced (Metoclopramide) [5] Drug-induced (Haloperidol) [5]
Meningeal enhancement after gadolinium injection Cortical atrophy, T2 multiple hyperintense white matter lesions Cerebral atrophy, T2 multiple hyperintense lesions T2 hyperintense lesions of basal ganglia
Disseminated cryptococcal infection (autopsy) Cerebral atrophy Cerebral atrophy, diffuse white matter abnormalities
6
0
5
Partial recovery Death
0
Isoniazid, Rifampicin, Pyrazinamide, Ethambutol, Dexamethasone
0
HAART, Levo-Dopa
0
n.d.
0
HAART, Levo-Dopa
Complete recovery
3
Withdrawal of Risperidone, Clonazepam n.d.
Partial recovery Death
Procyclidine, withdrawal of Metoclopramide Procyclidine, withdrawal of Haloperidol
Partial recovery Partial recovery
0 1 6
Complete recovery Death
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Table 1 (Continued ) Sex/age
Onset. Additional symptoms
Aetiology [Reference]
Neuroimaging
Years of AIDS
Treatment
Course
Tic
F/30
S. Headache, vomit, weight loss
T. gondii [22]
T2 hyperintense lesion of basal ganglia
0
Pyrimethamine, Sulphadiazine, Risperidone
Complete recovery
Tremor
M/35
A. Confusion, dysarthria
T. gondii [23]
0
S. Ataxia, nausea, vomit
Primary cerebral lymphoma [5]
HAART, Pyrimethamine, Sulphadiazine, Clonazepam, Trihexyphenidyl Radiotherapy, Dexamethasone
Complete recovery
M/33
T2 hyperintense, ringenhanced lesion of right thalamus and midbrain T2 hyperintense lesion in middle cerebellar peduncles
3
Death
M, male; F, female; A, acute; S, subacute; C: chronic; n.r., not reported; n.d., not done.
were significantly reduced and Haloperidol was gradually withdrawn. At 3 months follow-up general conditions strongly improved, movement disorders disappeared, and brain MRI only showed a 2 mm residual lesion in the midbrain. Furthermore HIV therapy was effective with a quantitative HIV-RNA assay of 1200 copies/mL and a CD4+ T lymphocytic subpopulation count of 530 cells/mL. Discussion Neurologic disorders are a well-known complication of late stage HIV and movement disorder incidence is estimated to be 2– 3% in HIV patients. A wide range of movement disorders has been described in HIV patients (Table 1), however choreic and Parkinsonian features are the most frequently reported [2–23]. Movement disorders have been more usually described in male, possibly because of gender differences in HIV prevalence. Several aetiologies need to be ruled out, including HIV subacute encephalopathy, HIV acute encephalitis, Cryptococcus spp, JC virus progressive multi-focal leukoencephalopathy, Mycobacterium tuberculosis, T. gondii, Streptococcus pneumoniae, Treponema pallidum, primary cerebral lymphoma, and metabolic and druginduced movement disorders [2–23]. We reported a case where subacute HC occurred as presenting symptom of HIV in a young female because of T. gondii subthalamic cerebral abscess, and a complete recovery was described. Chorea has been previously described in HIV patients with focal cerebral damage of subthalamus or its efferent pathways [1–4,6]. However there are several cases with diffuse cerebral involvement associated to choreic movements where it has been supposed the presence of additional factors such as a direct HIV effect on central dopaminergic pathways [2,7–10]. Autopsy studies confirmed that basal ganglia are early infiltrated by HIV-infected microglia and multinucleated giant cells. In consideration of this, HIV patients could be considered at risk of movement disorders that are precipitated by several stimuli such as basal ganglia toxoplasma abscess, metabolic disruptions or anti-dopaminergic drugs [1]. The prognosis of HIV patients with movement disorders seems to be not related to the movement phenomenology, but to the movement aetiology and in particular to the amount of cerebral damage. On one side a diffuse cerebral involvement relates to a poor prognosis. For instance JC virus progressive multifocal leukoencephalopathy-chorea is usually followed by death [2,5]. Furthermore HIV acute encephalitis and HIV subacute encephalopathy have been associated to chorea, Parkinsonism and cognitive symptoms, and HAART can induce only a partial regression of movement disorders [2,7–10]. On the other side non-structural cerebral movement disorders such as metabolic or drug-induced ones, are easily reversible [5,11,19]. Cerebral Toxoplasmosis can differently be involved in movement disorders and variable courses have been described. In particular death seems to occur in patients with diffuse cerebral
damage that can be associated with both multiple Toxoplasmosis abscesses and HIV encephalopathy [2,5]. Moreover a longer AIDS course is frequently associated to death because of several opportunistic infections worsening the clinical picture [2,5]. Patients with a single lesion (usually located in basal ganglia) can possibly recover completely from the movement disorder if an early and adequate treatment of T. gondii infection is performed [2– 4,22,23]. If the movement disorders persists a symptomatic treatment should be considered and additional factor could be hypothesized [22,23]. In particular a persistent toxoplasmosis abscess could irreversibly led to gliosis with loss of function of basal ganglia neurons [4,13]. In addition to this, the presence of cortical atrophy or multiple lesions could be indicative of HIV cerebral effect [5,8,18]. HAART does not seem to modify the movement disorder course in cerebral toxoplasmosis, however it is strongly suggested when AIDS diagnosis is performed [2,13,23]. No significant relation to the movement disorder course is found with gender, age, acute/subacute/chronic onset and/or additional symptoms. The good prognosis of our case should be related to the fact that the lesion was strictly isolated to basal ganglia and no AIDS additional features were found. Furthermore an effective treatment was started and a complete recovery was assessed by physicians and by MRI scans without continuing symptomatic treatment. In conclusion HIV should be considered in young patients with subacute movement disorder onset. A correct clinical overview is important since it may represent the initial feature of HIV infection and early treatment can led to a complete symptom relief. Disclosures On behalf of all authors, the corresponding author states that there is no conflict of interest. References [1] Tse W, Cersosimo MG, Gracies JM, Morgello S, Olanow CW, Koller W. Movement disorders and AIDS: a review. Parkinsonism and Related Disorders 2004;10(6):323–34. [2] Piccolo I, Causarano R, Sterzi R, Sberna M, Oreste PL, Moioli C, et al. Chorea in patients with AIDS. Acta Neurologica Scandinavica 1999;100(5):332–6. [3] Rabhi S, Amrani K, Maaroufi M, Khammar Z, Khibri H, Ouazzani M, et al. Hemichorea-hemiballismus as an initial manifestation in a Moroccan patient with acquired immunodeficiency syndrome and toxoplasma infection: a case report and review of the literature. The Pan African Medical Journal 2011;10:9. [4] Garretto NS, Bueri JA, Kremenchutzky M, Consalvo D, Segura M, Genovese O. Hemichorea associated with cerebral toxoplasmosis and AIDS. Arquivos de Neuro-Psiquiatria 1995;53(1):118–22. [5] Manji H, Sweeney B, Connolly S, Hughes A, Miller RF, Harrison MJ. Movement disorders in AIDS: infective, neoplastic and iatrogenic causes. Parkinsonism and Related Disorders 1995;1(1):13–9. [6] Pereira LS, Wu AP, Kandavel G, Memarzadeh F, McCulley TJ. Vitreitis and movement disorders associated with neurosyphilis and human immunodeficiency virus (HIV) infection: case report. Arquivos Brasileiros de Oftalmologia 2008;71(5):717–8. [7] Sporer B, Linke R, Seelos K, Paul R, Klopstock T, Pfister HW. HIV-induced chorea: evidence for basal ganglia dysregulation by SPECT. Journal of Neurology 2005;252(3):356–8.
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[8] Sankhla CS, Soman RN, Gupta NN, Shan PV. Movement disorder: a manifestation of HIV and its response to therapy. Neurology India 2009;57(6):789–91. [9] Gallo BV, Shulman LM, Weiner WJ, Petito CK, Berger JR. HIV encephalitis presenting with severe generalized chorea. Neurology 1996;46(4):1163–5. [10] Sevigny JJ, Chin SS, Milewski Y, Albers MW, Gordon ML, Marder KHIV. encephalitis simulating Huntington’s disease. Movement Disorders 2005;20(5): 610–3. [11] Brito MO, Doyle T. Movement and extrapyramidal disorders associated with interferon use in HIV/hepatitis C coinfection. AIDS 2007;21(14):1987–9. [12] Teive HA, Troiano AR, Cabral NL, Becker N, Werneck LC. Hemichorea-hemiballism associated to Cryptoccocal granuloma in a patient with AIDS: case report. Arquivos de Neuro-Psiquiatria 2000;58(3B):965–8. [13] Murakami T, Nakajima M, Nakamura T, Hara A, Uyama E, Mita S, et al. Parkinsonian symptoms as an initial manifestation in a Japanese patient with acquired immunodeficiency syndrome and Toxoplasma infection. Internal Medicine 2000;39(12):1111–4. [14] Maggi P, de Mari M, Moramarco A, Fiorentino G, Lamberti P, Angarano G. Parkinsonism in a patient with AIDS and cerebral opportunistic granulomatous lesions. Neurological Sciences 2000;21(3):173–6. ˜ a B, Rodriguez A, Martı´nez[15] De la Fuente-Aguado J, Bordo´n J, Moreno JA, Sopen Va´zquez C. Parkinsonism in an HIV-infected patient with hypodense cerebral lesion. Tubercle and Lung Disease 1996;77(2):191–2.
[16] Kobylecki C, Silverdale MA, Varma A, Dick JP, Kellet MW. HIV-associated Parkinsonism with levodopa-induced dyskinesia and response to highlyactive antiretroviral therapy. Movement Disorders 2009;23(16):2441–2. [17] Tanaka M, Endo K, Suzuki T, Kakita A, Takahashi H, Sata T. Parkinsonism in HIV encephalopathy. Movement Disorders 2000;15(5):1032–3. [18] Hersh BP, Rajendran PR, Battinelli D. Parkinsonism as the presenting manifestation of HIV infection: improvement on HAART. Neurology 2001;56(2): 278–9. [19] Kelly DV, Be´ı¨que LC, Bowmer MI. Extrapyramidal symptoms with ritonavir/ indinavir plus risperidone. Annals of Pharmacotherapy 2002;36(5):827–30. [20] Bouffard JP, Mena H, Ripple M, Troncoso J. Mesencephalic cryptococcal abscesses presenting with Parkinsonism as an initial manifestation of AIDS. Movement Disorders 2003;18(11):1354–7. [21] Jang W, Kim JS, Ahn JY, Kim HT. Reversible progressive supranuclear palsy-like phenotype as an initial manifestation of HIV infection. Neurological Sciences 2012;33(5):1169–71. [22] Aquino CC, Felı´cio AC, Godeiro-Junior C, Santos-Neto D, Pedroso JL, Oliveira AS, et al. Tic disorder: an unusual presentation of neurotoxoplasmosis in a patient with AIDS. Case Reports in Neurology 2010;2(3):145–9. [23] Lekoubou A, Njouoguep R, Kuate C, Kengne AP. Cerebral toxoplasmosis in Acquired Immunodeficiency Syndrome (AIDS) patients also provides unifying pathophysiologic hypotheses for Holmes tremor. BMC Neurology 2010;10:37.
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BAGA-97; No. of Pages 4 Basal Ganglia xxx (2013) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Basal Ganglia journal homepage: www.elsevier.com/locate/baga
Case report
Movement disorders as presenting symptoms of AIDS Marcello Moccia a, Marina Picillo a, Antonio Carotenuto a, Francesco Barbato a, Ivan Gentile b, Giuseppe Orefice a,* a b
Department of Neurosciences, University of Naples ‘‘Federico II’’, via Sergio Pansini 5, 80131 Napoli, Italy Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples ‘‘Federico II’’, via Sergio Pansini 5, 80131 Napoli, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 March 2013 Received in revised form 3 April 2013 Accepted 4 April 2013
Opportunistic infections are frequently reported to induce movement disorders in late stages of HIV. We report a case of a 32-year-old woman who presented headache and fever that was resistant to antipyretic drugs and to common antibiotics. Hereafter her right limbs were affected by several hyperkinetic movement disorders (ballismus, chorea, dystonia, athetosis). Brain MRI showed a mass lesion involving left basal ganglia. Serological tests were positive for HIV and for Toxoplasma gondii. Clinical features, therapeutical approaches, prognostic factors and possible pathogenesis are discussed. A literature review of cases of movement disorders associated with AIDS is provided. ß 2013 Elsevier GmbH. All rights reserved.
Keywords: HIV Toxoplasma gondii Movement disorders Chorea Ballismus AIDS
Introduction Movement disorders are frequently reported as a possible complication of Human Immunodeficiency Virus infection (HIV) and can rarely represent its initial manifestation [1]. Hemichorea (HC) is one of the most recurring HIV-related movement disorders, and is usually caused by basal ganglia lesions. Cerebral toxoplasmosis is a common opportunistic infection in Acquired Immune Deficiency Syndrome (AIDS) and its basal ganglia involvement may be complicated by a subacute onset of HC [2–4]. However HIVrelated movement disorders have several unsettled issues such as therapeutical approaches, prognostic factors and pathogenesis. Case report A 32-year-old women was admitted at our Department after one week from the onset of bilateral pulsating headache and fever (almost 101 8F) that seemed to be resistant to antipyretic drugs and to common antibiotics. In addition to this she complained of a subacute onset of hyperkinetic movement disorders in her right limbs (Video 1). The hyperkinetic movements affected proximal
Abbreviations: HIV, Human Immunodeficiency Virus infection; HC, Hemichorea; AIDS, Acquired Immune Deficiency Syndrome; HAART, Highly Active AntiRetroviral Therapy. * Corresponding author. Tel.: +39 081 746 2670; fax: +39 081 746 4348. E-mail address: orefi[email protected] (G. Orefice).
and distal muscles of the extremities and ranged from ballistic to choreic or athetotic movements with occasional dystonic jerks. No further signs were found at neurological examination. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.baga.2013.04.004. Brain MRI showed a mass lesion extending from left caudate to midbrain, with marked central necrotic component as for abscessual collection. The lesion presented a ring-enhancement after gadolinium administration. This lesion provoked third ventricle and midbrain dislocation with slight signs of transtentorial herniation. Serological tests were positive for HIV. The patient underwent further evaluations to assess the HIV state, in particular quantitative HIV-RNA assay (70,000 copies/mL) and CD4+ T lymphocytic subpopulation count (250 cells/mL) were performed. Highly Active Anti-Retroviral Therapy (HAART) was started with Tenofovir Disoproxil (245 mg/day) and Lopinavir/Ritonavir (400/100 mg/ day). Furthermore serological tests were positive for Toxoplasma gondii (T. gondii IgG 25 UI/mL with 1–4 as normal value; T. gondii IgM 0.01 UI/mL with <0.65 as normal value). A presumptive diagnosis of HIV-related cerebral Toxoplasmosis was performed and therapy was improved by adding Pyrimethamine (50 mg/day), Sulphadiazine (4 g/day), Desametazone (12 mg/day) and Glicerole (100 mg/day) to control both Toxoplasmosis infection and cerebral oedema. Moreover Haloperidol (3 mg/day) was prescribed for the hyperkinetic movement disorders. At 1 month follow-up brain MRI showed a reduction in size and enhancement of the lesion. Hyperkinetic movement disorders
2210-5336/$ – see front matter ß 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.baga.2013.04.004
Please cite this article in press as: Moccia M, et al. Movement disorders as presenting symptoms of AIDS. Basal Ganglia (2013), http:// dx.doi.org/10.1016/j.baga.2013.04.004
G Model
BAGA-97; No. of Pages 4 M. Moccia et al. / Basal Ganglia xxx (2013) xxx–xxx
2
Table 1 Movement disorders with clear aetiology in adult HIV patients.
Athetosis
Chorea
Sex/age
Onset. Additional symptoms
Aetiology [Reference]
Neuroimaging
Years of AIDS
Treatment
Course
M/55
S. Dysphasia
H. Zoster [5]
0
Acyclovir, Tetrabenazine
Partial recovery
F/33
S. n.r.
JC virus [5]
3
Cytosine arabinoside
Death
F/28
S. Headache, fever, weakness
T. gondii [5]
T2 multiple hyperintense lesions (internal capsule, left lentiform and subthalamic nuclei) T2 multiple hyperintense lesions Multiple CT hypodense lesions of thalami and lentiform nuclei
3
Pyrimethamine, Sulphadiazine
Death
M/28
S. Diarrhoea
Cryptococcus spp [12]
1
Fluconazole, Itraconazole
F/49
S. Behavioural abnormalities, dementia S. Behavioural abnormalities S. Dementia
HIV encephalitis [10]
Hypodense CT lesion of right subthalamus Cortical atrophy
0
n.d.
Partial recovery Death
Normal
2
T2 multiple hyperintense lesions (white matter, internal capsules) T2 multiple hyperintense lesions (pons, mesencephalon, internal capsule) T2 hyperintense lesion of subthalamic nucleus T2 multiple hyperintense lesions (mesencephalon, basal ganglia, thalamus, internal capsule, frontal operculum) T2 hyperintense lesion of capsule-talamic nuclei T2 hyperintense lesion of right cerebral peduncle, right frontal lobe, temporo-occipital area Normal
6
HAART (from 1 year), withdrawal of Interferon HAART
Complete recovery Complete recovery
1
n.d.
Death
1
HAART (from 1 year), Pyrimethamine, Sulphadiazine Phenobarbital, Fluconazole, Clindamycin
Complete recovery Death
0
TrimethoprimSulfamethoxazole Pyrimethamine, Sulphadiazine
Complete recovery Partial recovery
5
Withdrawal of Pentamidine
Complete recovery
0
Penicillin
n.r.
n.r.
Partial recovery Progressive course
0
HAART, Tetrabenazine
4
HAART, Acyclovir, Methylprednisolone
M/50 M/49
Drug-induced (Interferon) [11] HIV encephalopathy [2] JC virus [2]
M/27
A. Ataxia, weakness, impaired distal touch and pain sensitivity A. Fever
M/25
S. Fever
T. gondii [2]
F/59
T. gondii [3]
M/26
S. Headache, nausea, vomit, fever S. Seizures
F/28
A. n.r.
M/35 F/32
C. Ataxia, apraxia, dysarthria C. Dementia
M/47
C. Dementia
M/24
S. Behavioural abnormalities, confusion
Dyskinesias
M/36
A. Headache, fever, dysarthria
S. Pneumoniae [2]
Diffuse cerebral oedema
4
Ampicillin, Chloramphenicol
Death
Parkinsonism
M/65
C. Dementia
Cerebral atrophy
0
HAART, Levo-Dopa
M/49
S. Confusion
HIV encephalopathy [21] T. gondii [13]
0
M/31
S. Behavioural abnormalities C. Fever, asthenia, anorexia, weight loss
T2 hyperintense lesion of right lenticular nucleus Hypointense signal of left lenticular nucleus Hypodense CT lesion of left internal capsule, left external capsule and lower portion of lenticular nuclei T2 multiple hyperintense lesions Cortical atrophy, T2 multiple hyperintense lesions of frontal white matter T2 multiple hyperintense lesions of subcortical white matter Normal
HAART, Pyrimethamine, Clindamycin Ethambutol, Pyrazinamide
Partial recovery Partial recovery Progressive course Complete recovery
M/57
M/49
T. gondii [2]
T. gondii [4]
Metabolic (Pentamidine-induced Hypoglycaemia) [5] T. pallidum [6] HIV encephalopathy [7] HIV encephalopathy [8] HIV encephalitis [9]
M. tubercolosis [14] M. tubercolosis [15]
M/50
C. n.r.
M/63
S. Dementia
M/37
S. n.r.
HIV encephalopathy [18]
M/35
S. Tourette-like tics
M/63
C. Weight loss
Drug-induced (Risperidone) [19] Cryptococcus spp [20]
M/38
S. Nausea, vomit
M/29
S. Hypomania, anxiety
HIV encephalopathy [16] HIV encephalopathy [17]
Drug-induced (Metoclopramide) [5] Drug-induced (Haloperidol) [5]
Meningeal enhancement after gadolinium injection Cortical atrophy, T2 multiple hyperintense white matter lesions Cerebral atrophy, T2 multiple hyperintense lesions T2 hyperintense lesions of basal ganglia
Disseminated cryptococcal infection (autopsy) Cerebral atrophy Cerebral atrophy, diffuse white matter abnormalities
6
0
5
Partial recovery Death
0
Isoniazid, Rifampicin, Pyrazinamide, Ethambutol, Dexamethasone
0
HAART, Levo-Dopa
0
n.d.
0
HAART, Levo-Dopa
Complete recovery
3
Withdrawal of Risperidone, Clonazepam n.d.
Partial recovery Death
Procyclidine, withdrawal of Metoclopramide Procyclidine, withdrawal of Haloperidol
Partial recovery Partial recovery
0 1 6
Complete recovery Death
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Table 1 (Continued ) Sex/age
Onset. Additional symptoms
Aetiology [Reference]
Neuroimaging
Years of AIDS
Treatment
Course
Tic
F/30
S. Headache, vomit, weight loss
T. gondii [22]
T2 hyperintense lesion of basal ganglia
0
Pyrimethamine, Sulphadiazine, Risperidone
Complete recovery
Tremor
M/35
A. Confusion, dysarthria
T. gondii [23]
0
S. Ataxia, nausea, vomit
Primary cerebral lymphoma [5]
HAART, Pyrimethamine, Sulphadiazine, Clonazepam, Trihexyphenidyl Radiotherapy, Dexamethasone
Complete recovery
M/33
T2 hyperintense, ringenhanced lesion of right thalamus and midbrain T2 hyperintense lesion in middle cerebellar peduncles
3
Death
M, male; F, female; A, acute; S, subacute; C: chronic; n.r., not reported; n.d., not done.
were significantly reduced and Haloperidol was gradually withdrawn. At 3 months follow-up general conditions strongly improved, movement disorders disappeared, and brain MRI only showed a 2 mm residual lesion in the midbrain. Furthermore HIV therapy was effective with a quantitative HIV-RNA assay of 1200 copies/mL and a CD4+ T lymphocytic subpopulation count of 530 cells/mL. Discussion Neurologic disorders are a well-known complication of late stage HIV and movement disorder incidence is estimated to be 2– 3% in HIV patients. A wide range of movement disorders has been described in HIV patients (Table 1), however choreic and Parkinsonian features are the most frequently reported [2–23]. Movement disorders have been more usually described in male, possibly because of gender differences in HIV prevalence. Several aetiologies need to be ruled out, including HIV subacute encephalopathy, HIV acute encephalitis, Cryptococcus spp, JC virus progressive multi-focal leukoencephalopathy, Mycobacterium tuberculosis, T. gondii, Streptococcus pneumoniae, Treponema pallidum, primary cerebral lymphoma, and metabolic and druginduced movement disorders [2–23]. We reported a case where subacute HC occurred as presenting symptom of HIV in a young female because of T. gondii subthalamic cerebral abscess, and a complete recovery was described. Chorea has been previously described in HIV patients with focal cerebral damage of subthalamus or its efferent pathways [1–4,6]. However there are several cases with diffuse cerebral involvement associated to choreic movements where it has been supposed the presence of additional factors such as a direct HIV effect on central dopaminergic pathways [2,7–10]. Autopsy studies confirmed that basal ganglia are early infiltrated by HIV-infected microglia and multinucleated giant cells. In consideration of this, HIV patients could be considered at risk of movement disorders that are precipitated by several stimuli such as basal ganglia toxoplasma abscess, metabolic disruptions or anti-dopaminergic drugs [1]. The prognosis of HIV patients with movement disorders seems to be not related to the movement phenomenology, but to the movement aetiology and in particular to the amount of cerebral damage. On one side a diffuse cerebral involvement relates to a poor prognosis. For instance JC virus progressive multifocal leukoencephalopathy-chorea is usually followed by death [2,5]. Furthermore HIV acute encephalitis and HIV subacute encephalopathy have been associated to chorea, Parkinsonism and cognitive symptoms, and HAART can induce only a partial regression of movement disorders [2,7–10]. On the other side non-structural cerebral movement disorders such as metabolic or drug-induced ones, are easily reversible [5,11,19]. Cerebral Toxoplasmosis can differently be involved in movement disorders and variable courses have been described. In particular death seems to occur in patients with diffuse cerebral
damage that can be associated with both multiple Toxoplasmosis abscesses and HIV encephalopathy [2,5]. Moreover a longer AIDS course is frequently associated to death because of several opportunistic infections worsening the clinical picture [2,5]. Patients with a single lesion (usually located in basal ganglia) can possibly recover completely from the movement disorder if an early and adequate treatment of T. gondii infection is performed [2– 4,22,23]. If the movement disorders persists a symptomatic treatment should be considered and additional factor could be hypothesized [22,23]. In particular a persistent toxoplasmosis abscess could irreversibly led to gliosis with loss of function of basal ganglia neurons [4,13]. In addition to this, the presence of cortical atrophy or multiple lesions could be indicative of HIV cerebral effect [5,8,18]. HAART does not seem to modify the movement disorder course in cerebral toxoplasmosis, however it is strongly suggested when AIDS diagnosis is performed [2,13,23]. No significant relation to the movement disorder course is found with gender, age, acute/subacute/chronic onset and/or additional symptoms. The good prognosis of our case should be related to the fact that the lesion was strictly isolated to basal ganglia and no AIDS additional features were found. Furthermore an effective treatment was started and a complete recovery was assessed by physicians and by MRI scans without continuing symptomatic treatment. In conclusion HIV should be considered in young patients with subacute movement disorder onset. A correct clinical overview is important since it may represent the initial feature of HIV infection and early treatment can led to a complete symptom relief. Disclosures On behalf of all authors, the corresponding author states that there is no conflict of interest. References [1] Tse W, Cersosimo MG, Gracies JM, Morgello S, Olanow CW, Koller W. Movement disorders and AIDS: a review. Parkinsonism and Related Disorders 2004;10(6):323–34. [2] Piccolo I, Causarano R, Sterzi R, Sberna M, Oreste PL, Moioli C, et al. Chorea in patients with AIDS. Acta Neurologica Scandinavica 1999;100(5):332–6. [3] Rabhi S, Amrani K, Maaroufi M, Khammar Z, Khibri H, Ouazzani M, et al. Hemichorea-hemiballismus as an initial manifestation in a Moroccan patient with acquired immunodeficiency syndrome and toxoplasma infection: a case report and review of the literature. The Pan African Medical Journal 2011;10:9. [4] Garretto NS, Bueri JA, Kremenchutzky M, Consalvo D, Segura M, Genovese O. Hemichorea associated with cerebral toxoplasmosis and AIDS. Arquivos de Neuro-Psiquiatria 1995;53(1):118–22. [5] Manji H, Sweeney B, Connolly S, Hughes A, Miller RF, Harrison MJ. Movement disorders in AIDS: infective, neoplastic and iatrogenic causes. Parkinsonism and Related Disorders 1995;1(1):13–9. [6] Pereira LS, Wu AP, Kandavel G, Memarzadeh F, McCulley TJ. Vitreitis and movement disorders associated with neurosyphilis and human immunodeficiency virus (HIV) infection: case report. Arquivos Brasileiros de Oftalmologia 2008;71(5):717–8. [7] Sporer B, Linke R, Seelos K, Paul R, Klopstock T, Pfister HW. HIV-induced chorea: evidence for basal ganglia dysregulation by SPECT. Journal of Neurology 2005;252(3):356–8.
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Please cite this article in press as: Moccia M, et al. Movement disorders as presenting symptoms of AIDS. Basal Ganglia (2013), http:// dx.doi.org/10.1016/j.baga.2013.04.004