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BRIEF COMMUNICATIONS: D.J.L. MacGowan, S.N. Scelsa, and M. Waldron An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy Neurology 2001; 57: 1094-1097 [Abstract] [Full text] [PDF]

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Reply to both Letters to the Editor

Daniel Mac Gowan   (15 March 2002)

An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy

H J v Giesen, R Kaiser, H Koller, K Wetzel, G Arendt   (15 March 2002)

An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy

Lawrence A Cone   (15 March 2002)

Reply to both Letters to the Editor 15 March 2002
Daniel Mac Gowan Beth Israel Medical Center New York Send Correspondence to journal: Re: Reply to both Letters to the Editor DMacGow{at}bethisraelny.org Daniel Mac Gowan	The authors appreciate the interesting letter by Cone et al. reporting HHV-8 seropositivity in 5/5 HIV-negative ALS patients with different concomitant medical problems. This raises the possibility that motor neuron disease in our HIV positive patient might have been due to an opportunistic pathogen. This was supported by the finding of a brachium pontis white matter lesion and a higher than expected CSF protein for an HIV positive patient. However, we performed two lumbar punctures with negative bacterial, fungal and viral culture as well as negative pcr for JC and CMV viral DNA. We believe that HIV itself can cause motor neuron disease and that the brachium pontis abnormality in our patient was due to co-morbid progressive multifocal leukoencephalopathy. Nevertheless, in response to this interesting finding, we will also plan to test our patient’s blood for HHV-8 antibodies and antigen. Is response to the letter from Giesen et al., I would like to point out that the first patient should be classified as having benign fasciculations rather than ALS or motor neuron disease given the absence of weakness, objective upper motor neuron signs, and denervation on EMG. In addition, the second patient is alleged to have ALS but no clinical, electrophysiologic or imaging information is provided. Therefore, it is difficult to comment on these cases’ relevance to current interest on retroviruses in ALS. Lastly, subtype B HIV-1 infection is by far the most common HIV-1 genotype in the community, particularly in the U.S., and sequence homology between the samples does suggest that both patients were infected by the same HIV-1 genotype. This fact would be interesting if both these cases were provided with more information showing that they actually have ALS-like disorder.
An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy 15 March 2002
H J v Giesen Heinrich-Heine-Universitat Dusseldorf Germany, R Kaiser, H Koller, K Wetzel, G Arendt Send Correspondence to journal: Re: An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy giesenhj{at}uni-duesseldorf.de H J v Giesen, et al.	Moulignier et al. recently had published [1] a series of six HIV-1 seropostitive (+) patients with a neurologic disorder mimicking amyotrophic lateral sclerosis (ALS). This disorder was reversible under HIV-1 specific highly active antiretroviral therapy (HAART), which suggested that HIV-1 itself might play a role in the neuropathogenesis. A similar case clearly responsive to HAAT has been published in the same issue. [2] This observation has prompted an editorial [3] in which a possible viral aetiology for ALS has been reviewed and newly debated. In July 2001, a 44-year-old homosexual man was presented in our department. He was known to be HIV-1 (+) since 1991 (CDC stage B2 with history of herpes zoster, CD 4 cell count 430 cells/ul, plasma viral load 12.000 copies/ml). He was naïve to any antiretroviral therapy and complained of ubiquitous fasciculations and muscle cramps. Fasciculations were observed in both quadriceps muscles. His deep tendon reflexes were brisk, but not exaggerated. The neurologic examination was otherwise normal. Electroneurography excluded polyneuropathy and multifocal conduction block, electromyography revealed fasciculations not only in the quadriceps muscle, but also in the anterior tibial and the biceps brachii muscle, but no signs of active denervation. The history of the patient was remarkable in so far as his HIV-1 (+) partner had been diagnosed to suffer from ALS with its characteristic clinical and electrophysiological features. He first complained of fasciculations in May 2000, followed by progressive weakness and atrophy. The HIV-1 infection was diagnosed in April 2000 (CDC stage A2 CD 4 cell count 447 cells/ul, plasma viral load 21,857 copies/ml). Symptoms deteriorated progressively despite newly started HAART with zidovudine, lamivudine and nevirapine. Sequence analysis form HIV reverse transcriptase and protease revealed that both patients showed HIV-1 subtype B and a sequence homology which is higher to each other compared to other HIV-strains. This implies infections with identical HIV-strains. These cases suggest not only that viral quasispecies may indeed play a role in HIV-1 associated ALS like disorders, but also that the presence of defined HIV-1 strains may be a prerequisite for the later development of such a disease. This does not imply that other neuropathogenetic mechanisms are less important for the further course of the disease. Every patient presented with ALS like symptoms should be tested for HIV-1 because of a potential therapeutical option and HIV-1 viral quasispecies should be determine in HIV-1 (+) patients to identify possible preferential viral strains. References: 1)Moulignier A, Moulonguet A, Pialoux G, Rozenbaum W. Reversible ALS- like disorder in HIV infection. Neurology 2001;57:995-1001. 2)MacGowan DJ, Scelsa SN, Waldron M. An AlS-like syndrome with new HIV infection and complete response to antiretroviral therapy. Neurology 2001;57:1094-1097. 3)Jubelt B, Berger JR. Does viral disease underlie ALS? Lessons from the AIDS pandemic. Neurology 2001;57:945-946.
An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy 15 March 2002
Lawrence A Cone Eisenhower Medical Center Rancho Mirage CA Send Correspondence to journal: Re: An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy radhika_andavolu{at}hotmail.com Lawrence A Cone	Two recent papers by Moulignier et al [1] and MacGowen et al [2] in Neurology present clinical and laboratory evidence of a probable increased incidence of amyotrophic lateral sclerosis (ALS) in patients infected by human immunodeficiency viruses (HIV)-1 and –2. Several possible mechanisms were suggested including direct neuronal damage, disease due to cytokine production and autoimmunity. The fact that symptoms and signs of ALS improved with antiretroviral therapy implied that the effect was specifically upon HIV induced disease. However, Kaposi’s sarcoma (KS) which now appears almost certainly to be due to human herpesvirus-8 (HIV- 8) also often disappears with antiretroviral therapy. It is more than passing interest that up to 35% of homosexual men with the acquired immunodeficiency syndrome demonstrates antibodies to HHV-8 [3], while they are present in less than 4% of US blood donors. [3] We have recently had an opportunity to study HHV-8 antibody levels in five non-HIV+ patients with ALS. Two of five were women, one was black and all five had associated medical disorders including, monoclonal gammopathy, and lymphoma of the lung, scleroderma, osteoarthritis and hyperlipidemia. Their ages ranged from 70 to 81 years. Three ultimately dies of aspiration pneumonia. Antibody titers as measured by indirect immunofluorescence using the BCP-1 cell line [4] were positive in all patients and ranged from 1:20 to 1:60. HHV-8 in blood by PCR was identified in only one patient. The presence of HHV-8 antibody in all of our patients in this small study would suggest that this may also be the case in patients with AIDS and ALS. Since AIDS-related KS often improves with antiretroviral therapy, the improvement in ALS with such therapy may be due to an effect upon HHV- 8 as well. Histopathologically, death of neurons in ALS is preceded by perikaryal shrinkage, the formation of webs of ubiquitin-positive threads [5] and axonal swellings staining for ubiquitin and alpha-synuclein. Over the years multiple causes of ALS have been invoked, particularly a viral etiology. The presence of a homologue of interleukin-6 in HHV-8 with 24.8% amino acid identity suggests that this viral cytokine could play a role in the pathogenesis of HHV-8 related diseases. REFERENCES 1. Moulignier A, Moulonguet A, Pialoux G, Rezenbaum W. Reversible ALS -like disorder in HIV infection. Neurology 2001; 57: 995-1001. 2. MacGowen DLJ, Scelsa SN, Waldron M. An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy. Neurology 2001; 57: 1094-1097. 3. Gao S-J, Kingsley L, Li M, et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi’s sarcoma. Nature Med 1996; 2: 925-927. 4. Boshoff C, Gao S-J, Healey LE et al. Establishment of a KSHV positive cell line (BCP-1) from peripheral blood and characterizing its growth in vivo. Blood 1998; 91: 1671-1679. 5. Martin JB. Molecular basis of the neurodegenerative disorders. N Engl J Med 1999; 340: 1070-1079.