Motor neuron diseases
Clinical features
Several reports indicate that different motor neuron diseases (MNDs),
such as amyotrophic lateral sclerosis (ALS), primary lateral sclerosis
(PLS), or progressive muscular atrophy (PMA) may develop coincidentally
with a cancer. However, is still controversial whether these different
forms of MND can be considered paraneoplastic
Motor neuron involvement and anti-Hu syndrome
Most authors agree that motor neuron disease, predominantly the involvement
of both upper and lower motor neuron, may be related to paraneoplastic
encephalomyelitis (PEM). Up to 20% of patients affected by PEM show
signs of dysfunction at different levels of the motor system during
the evolution of the disease and in some instances these may represent
the initial manifestation of the syndrome. These patients, that usually
harbour anti Hu-antibodies, invariably
develop other neurological signs, and do not differ from PEM patients
without signs of motor neuron disease concerning the associated tumor
type, mostly small cell lung cancer, as well as the evolution of the
disease and the prognosis.
Amyotrophic lateral sclerosis (ALS)
ALS is a degenerative disease affecting both upper and lower motor neurons
that has been seldom observed in oncological patients. Occasionally
a patent remission, or at least a significant improvement of the neurological
syndrome has been related to cancer treatment. Nonetheless, the available
evidence does not allow to draw any conclusion about a relationship
linking ALS and cancer. Oncological patients affected by ALS do not
differ from patients with sporadic ALS: they do not express anti-neuronal
antibodies, usually die as a consequence of motor neuron defiance with
a comparable survival. Cancer treatment usually does not improve neurological
status. On the contrary, tumor progression might be slower in patients
with concomitant ALS. To date, the World Neurological Association does
not recognize the existence of paraneoplastic ALS (El
Escorial Criteria for ALS, 1998).
Primary lateral sclerosis (PLS)
Primary lateral sclerosis consists in pure involvement of the upper
motor neurons. It is a rare disease which is frequently observed in
women with a breast cancer. For this reason, so far PLS is the MND with
the highest probability of having a paraneoplastic origin. The course
of PLS in cancer patients is chronic and progressive, and it may turn
into a fully expressed ALS. The coexistent cancer does not modify PLS
progression. Although PLS is not yet recognized as a “classical
paraneoplastic syndrome”, a mammography in all women who have
a UMN syndrome resembling PLS is warranted.
Progressive muscular atrophy (PMA)
This syndrome was described in patients with Hodgkin’s and non-Hodgkin’s
lymphoma and called subacute motor neuronopathy. The disorder is characterized
by subacute progressive, painless, and often asymmetrical lower motor
neuron weakness, occasionally accompanied by minor sensory symptoms.
The evolution of the neurological disease is independent from the course
of the cancer. Some patients also experience spontaneous improvement
with normalization of the neurological examination. It is still under
discussion whether PMA associated with lymphoma could be related to
this cancer. At the moment, similarly to ALS, the World Association
of Neurology does not recognize the existence of a paraneoplastic PMA.
Motor neuron diseases and lymphoproliferative
disorders
Patients affected by lymphoproliferative disease (Waldestrom’s
macroglobulinemia, multiple myeloma, chronic lymphocytic leukaemia,
follicular cell lymphoma, and Hodgkin’s disease) (LPD) can develop
a MND (ALS, PLS and PMA). There has been no case-control study to establish
the frequency of this association, but some authors suggest that LPD
is disproportionately frequent in MND patients compared with the general
population. However, the association of MND and LPD could be a coincidence.
The diagnosis of MND in LPD patients implies a poor prognosis due to
MND progression, which is not usually affected by the treatment of the
lymphoproliferative disease.
Selected references
1. Gordon PH, Rowland LP, Younger DS; Sherman WH; Hays AP; Louis ED,
Trojaborg, W, Lovelace RE; Murphy PL; Latov N: Lymphoproliferative disorders
and motor neuron disease: An update. Neurology 48:1671-1675, 1997
2. Forsyth PS, Dalmau J, Graus F, Cwik V, Rosemblum MK, Posner JB: Motor
neuron syndromes in cancer patients. Ann Neurol 41: 722-730, 1997
3. Rowland LP: Paraneoplastic Primary Lateral Sclerosis and Amyotrophyc
Lateral Sclerosis. Ann Neurol 41:703-705, 1997
4. World Federation of Neurology: Revised criteria for the diagnosis
of ALS. http//www.wfnals.org/Articles/elescorial1998criteria.htm
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