Table Of ContentActa Myologica • 2011; XXX: p. 29-31
HIV-related neuromuscular diseases:
nemaline myopathy, amyotrophic lateral
sclerosis and bibrachial amyotrophic diplegia
L.P. Rowland
Neurological Institute, Columbia University Medical Center, New York, NY, USA
The human immunodeficiency virus (HIV) causes diverse dis- festations. It was named by G. Milton Shy, W. King Engel
orders of the brain, spinal cord and peripheral nerves. Rarely, and their associates in 1963 (1). “Nemaline” was applied
polymyositis and myoglobinuria are seen. Two other neuromus-
because muscle biopsies showed deposits of thread-like
cular syndromes in people with HIV antibodies are nemaline
structures; the word came from the Greek “nema”. The
myopathy and bibrachial amyotrophic diplegia, a form of mo-
tor neuron disease. The associations between these diseases and threads were dark red with the Gomori stain and contain
the possibility that HIV infection could be a risk factor for either actin. The clinical syndromes are seen most often in in-
amyotrophic lateral sclerosis (ALS) itself or other motor neuron fants and children (2, 3). One form, however, occurs in
diseases are investigated.
adults, warranting the name “sporadic late onset nemaline
myopathy” (SLONM) (4).
Key words: HIV-Related Neuromuscular Diseases, nemaline myop-
In infants and children, the disease is often familial
athy, amyotrophic lateral sclerosis, bibrachial amyotrophic diplegia
in a pattern consistent with autosomal recessive inherit-
ance. In adults, the disease is almost always sporadic and
is seen in association with other conditions (2). Here, we
Introduction
are considering the association of SLONM with HIV in-
The human immunodeficiency virus (HIV) causes fection.
diverse disorders of the brain, spinal cord and peripheral
“Sporadic Late-onset Nemaline Myopathy” (SLONM)
nerves. Rarely, polymyositis and myoglobinuria are seen.
Two other neuromuscular syndromes in people with HIV Clinical Manifestations: SLONM affects both sexes
antibodies are nemaline myopathy and bibrachial amyo- equally at ages ranging from 20 to 50. The most com-
trophic diplegia, a form of motor neuron disease. These mon clinical syndrome is one of proximal limb weakness
associations have not been proven epidemiologically and
of subacute onset and progression, sometimes severe and
it is uncertain whether HIV infection is a risk factor for
disabling. The neck extensors may be affected, resulting
either amyotrophic lateral sclerosis (ALS) itself or other
in the dropped head syndrome. Dysphagia and respiratory
motor neuron diseases. However, manifestations of ALS
failure may appear. Tendon reflexes are usually absent.
in people with HIV infection can be treated effectively
Fasciculation is not often seen but may be. Sometimes
with Highly Active Antiretroviral Therapy (HAART),
there is evidence of a second muscle disorder, which may
which would therefore be expected to lower the rate at
be dermatomyositis or polymyositis. Progressive external
which new cases appear.
ophthalmoplegia was reported in two patients (5, 6). The
association with HIV was first described by Dalakas and
Nemaline Myopathy
associates (7). It is not clear how often patients with ne-
History: Drs. Engel and Askanas have been leaders in maline disease are HIV-positive.
the study of nemaline myopathy and other conditions in Laboratory Findings: Diagnostic studies are usually
which abnormal inclusions are found in muscle. Nemaline indicative of myopathy but sometimes show evidence of
myopathy is defined by the clinical and histologic mani- denervation. By definition, the muscle biopsy must show
Address for correspondence: Lewis P. Rowland, M.D., Neurological Institute, 710 West 168th Street, Columbia University Medical
Center, New York, NY 10032, USA. E-mail: [email protected]
29
L.P. Rowland
the deposits, which are seen as dark red. At the Mayo cated than ALS, with signs of inflammation or vacuolar
Clinic, Chahin et al. (2) examined 3-µm-thick frozen myelopathy (22 23).
sections stained trichromatically or immunostained for But the most remarkable difference from ALS was
α-actinin or myotilin. Electron microscopy in 12 cases the reversal of symptoms by treatment with nucleosides
identified the rods in all and revealed additional structural or HAART (24-26). Some of these patients returned to
abnormalities. CK values were normal or low. Seven of normal neurologically. However, one patient’s symptoms
their 14 patients had monoclonal gammopathy and were progressed despite HAART therapy and we have seen
followed for 1 to 5 years; five died of respiratory fail- one woman whose symptoms started after she had been
ure. Five patients without monoclonal gammopathy were on therapy for one year.
followed for 4 to 23 years and none died of the disease. Therefore ALS in HIV-positive people may take
The presence of gammopathy therefore may be ominous. either of two forms, one that responds to HAART and
HIV was excluded in 3 of 6 patients and the other 3 were another that does not. The responsive form seems to be
deemed to have no HIV risk factors. related to viral infection. Harbingers of therapeutic re-
In other reports, a patient with monoclonal gammopa- sponse are young age at onset, progression in days or
thy had features of both nemaline disease and “trabecular” weeks, and abnormal CSF. The unresponsive form may
or “lobulated” muscle fibers as well as biclonal gammopa- be “ordinary” sporadic ALS that occurs by chance in an
thy (8). Another patient was being treated for dermatomy- HIV-positive person.
ositis when muscle biopsy showed nemaline rods (9). A purely upper motor neuron syndrome has also
Therapy: Immunosuppressive therapy with melpha- been reported in two HIV-positive patients. One proved to
lan, intravenous immunoglobulins (IVIG) or both may have progressive multifocal leucoencephalopathy (PML)
be helpful (2, 10-12) . Prednisone is sometimes effec- but the other was compatible with primary lateral sclero-
tive (13, 14) but was uniformly ineffective in the Mayo sis (27). Two other patients had PML (28). A second vari-
report (2). Autologous stem therapy has also brought ben- ation of motor neuron disorder is “brachial amyotrophic
efit (15, 16). Long term immunosuppression with rituxi- diplegia”, which may affect HIV-positive people (29-31)
mab may be considered. Physical therapy is also indicated (“man-in-a-barrel syndrome”) and one patient showed
to maintain gait and general strength. lingual fasciculation with hyperreflexia; postmortem ex-
amination showed sarcoid brainstem encephalitis (32).
In contrast, one patient had the lower motor neuron syn-
HIV and Motor Neuron Diseases
drome of progressive muscular atrophy (33). One patient
In 1985, the fourth year of the emerging AIDS epi- with brachial amyotrophy had an SOD1 mutation (34).
demic, Hoffman et al. (17) described a 26 year old man Recognition of these HIV-related motor neuron syn-
with both upper and lower motor neuron signs. He was dromes is important because they may respond to treat-
still alive a year later. Many feared there would be an ment. These syndromes also raise theoretical issues –
epidemic of viral ALS. However, that fear was never whether sporadic ALS could ever be caused by a virus or
realized. By mid-2002, there had been reports of 19 autoimmunity. It is still not known how HIV might cause
patients with motor neuron disorders, with no evidence a motor neuron disorder (35).
that HIV infection increases the likelihood of devel-
oping ALS. 13 of the 19 clearly had a disorder that
Conclusion
was unlike ALS in one major way, the rapidity of pro-
gression. The time from onset of symptoms to severe Both nemaline myopathy and motor neuron disease
handicap was measured in weeks and not months, too may be associated with HIV. Treatment of the myopathy
rapid for conventional ALS. One patient died 3 months with prednisone may or may not be effective but can be
after onset (18). tried. HAART may be neurologically effective in HIV
This HIV-related disorder differed in other ways, patients with ALS. These responses to treatment warrant
too. The patients were younger than most cases of mo- consideration in planning diagnostic studies.
tor neuron disease; only 2 of the 13 were older than age
40 while only 10% of all cases of ALS begin before that
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