This work was supponed by the Jay Slotkin Fund for ~~~~~~~~d~~of a demyelinating process, with conduction blocks, reduction in conduction velocity, abnormal temporal dispersion, Research and the Muscular Dystrophy Association. We appreciate the help of Blair Ertel.
Department of Neurology TheJohns Hopkin’ University School of Medicine Baltimore, M D
References 1. Rothstein JD, Tsai G, Kuncl RW, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 199U;28:18-25 2. Perry TL, Geiger C, Hansen S, Eisen A. Amyotrophic lateral sclerosis: amino acid levels in plasma and cerebrospinal fluid. Ann Neurol 1990;28:12-17 3. Perry TL, Hansen S, Kennedy J. CSF amino acids and plasmaCSF amino acid ratios in adults. J Neurochem 1975;24:587-589 4. Spink DC, Swam JW, Snead OC, et al. Analysis of aspartate and glutamate in human cerebrospinal fluid by high-performance liquid chromatography with automated precolumn derivatization. Anal Biochem 1986;158:79-86 5. Spink C, Martin DL. Excitatory amino acids in amyotrophc lateral sclerosis (letter). Ann Neurol 1991;29:110 6. Lundqvist C, Blomstrand C, Hamberger A, Wikkelso C. Liquid chromatographic separation of cerebrospinal fluid amino acids after precolumn fluorescence derivatization. Acta Neurol Scand 1989;79:273-279
Diagnosis of Amyotrophic Lateral Sclerosis Andreas Steck, MD, and Th. Kuntzer, M D Never before has the need for internationally acceptable criteria for the diagnosis of amyotrophic lateral sclerosis (ALS) 111been so obvious as now, when clinical and basic research on motor neuron disorders is moving at such a rapid pace. The current tendency, supported by some, to consider ALS an heterogeneous condition with more than one etiology has blurred rhe definition of the disease described by Charcot. The recent paper by Santoro and colleagues [2] is a good example of that trend. This elegant work makes a major contribution toward identifying the pathogenesis of multifocal conduction block in patients with anti-GM 1 antibodies. However, by labeling their patient’s condition ALS, Santoro and associates give the message that ALS-a progressive neurodegenerative disease involving motor neurons in the cerebral cortex, brainstem, and spinal cord-may be caused by anti-GM1 antibodies directed to the nodes of Ranvier. The authors know well that many conditions can mimic ALS and that the presence of brisk reflexes in the upper extremities, as reported in their patient, is not an unequivocal sign of a primary motor neuron degeneration. As a matter of fact, this patient has many findings inconsistent with the diagnosis of ALS. Those are particularly well demonstrated by the electrophysiologic abnormalities. In this case, there is evidence of a predominant motor peripheral neuropathy fulfilling criteria
and absent F-waves [3]. The mild sensory involvement is demonstrated by the difference in sural nerve amplitude and the findings of immunoglobulins at nodes of Ranvier in the surd nerve biopsy. The development of a progressive weakness after a rabies vaccine could suggest a diagnosis of a postinfectious polyradiculopathy, possibly with some degree of central involvement [4].While it may be intriguing to consider that a motor system degeneration may be caused by anti-GM1 antibodies binding at the nodes of Ranvier and possibly at other neuronal structures as well, we disagree with the diagnosis of ALS in this patient, for which there is little supportive evidence. Such a diagnosis will, we are sure, confuse many readers.
Department of Neurology CHU Vaudoi’, Lauxanne Switzerland
References 1. World Federation of Neurology Subcommittee on Motor Neuron Disease. El Escorial criteria for diagnosis of amyotrophic lateral sclerosis. Presented at the VIIth International Congress on Neuromuscular Diseases, Munich, Germany, September 16-22,
1990 2. Santoro M, Thomas FP, Fink ME, et al. IgM deposits at nodes of Ranvier in a patient with amyotrophic lateral sclerosis, anti-GM 1 antibodies and multifocal motor conductiun block. Ann Neurol 1990;28:373-377 3. Cornblath DR. Electrophysiology in Guillain-Barri. syndrome. Ann Neurol 199U;27(suppl):S17-S20 4. Hemachudha T, Phanaphak P, Johnson RT, et a]. Neurologic complication of Semple-type rabies vaccine: clinical and immunologic studies. Neurology 1387;37:550-556
Reply
Lewis P. Rowland, MD, Maria Santoro, MD, Dale J. Lange, MD, Arthur P. Hays, MD,” F. Thomas, MD, M. E. Fink, MD, N. Wadia, MD, and N. Latov, MD, PhD Drs Steck and Kuntzer raise important issues. Dr Rowland joins the authors in replying because he suggested using “ALS” in the title of our paper.
Diagnosis of ALS Clinical diagnosis [If is based on adult onset of progressive disability with signs of lower motor neuron dysfunction in all cases, sparing sensation. If only lower motor neurons are affected clinically, the term is progressive spinal muscular atrophy. The term “ALS” is reserved for patients who also have definite upper motor neuron signs. Active tendon reflexes in limbs with fasciculating, wasted muscles are “probable upper motor neuron signs.” There has never been a formal evaluation of the accuracy of the clinical diagnosis of ALS. The only way to prove the diagnosis is by postmortem examination; even that may not give unequivocal answers. From personal experience, the reliability of clinical diagnosis probably exceeds 95 96.
Annals of Neurology
Vol 30 No 2
August 1991 225
Department of Neurology TheJohns Hopkin’ University School of Medicine Baltimore, M D
References 1. Rothstein JD, Tsai G, Kuncl RW, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 199U;28:18-25 2. Perry TL, Geiger C, Hansen S, Eisen A. Amyotrophic lateral sclerosis: amino acid levels in plasma and cerebrospinal fluid. Ann Neurol 1990;28:12-17 3. Perry TL, Hansen S, Kennedy J. CSF amino acids and plasmaCSF amino acid ratios in adults. J Neurochem 1975;24:587-589 4. Spink DC, Swam JW, Snead OC, et al. Analysis of aspartate and glutamate in human cerebrospinal fluid by high-performance liquid chromatography with automated precolumn derivatization. Anal Biochem 1986;158:79-86 5. Spink C, Martin DL. Excitatory amino acids in amyotrophc lateral sclerosis (letter). Ann Neurol 1991;29:110 6. Lundqvist C, Blomstrand C, Hamberger A, Wikkelso C. Liquid chromatographic separation of cerebrospinal fluid amino acids after precolumn fluorescence derivatization. Acta Neurol Scand 1989;79:273-279
Diagnosis of Amyotrophic Lateral Sclerosis Andreas Steck, MD, and Th. Kuntzer, M D Never before has the need for internationally acceptable criteria for the diagnosis of amyotrophic lateral sclerosis (ALS) 111been so obvious as now, when clinical and basic research on motor neuron disorders is moving at such a rapid pace. The current tendency, supported by some, to consider ALS an heterogeneous condition with more than one etiology has blurred rhe definition of the disease described by Charcot. The recent paper by Santoro and colleagues [2] is a good example of that trend. This elegant work makes a major contribution toward identifying the pathogenesis of multifocal conduction block in patients with anti-GM 1 antibodies. However, by labeling their patient’s condition ALS, Santoro and associates give the message that ALS-a progressive neurodegenerative disease involving motor neurons in the cerebral cortex, brainstem, and spinal cord-may be caused by anti-GM1 antibodies directed to the nodes of Ranvier. The authors know well that many conditions can mimic ALS and that the presence of brisk reflexes in the upper extremities, as reported in their patient, is not an unequivocal sign of a primary motor neuron degeneration. As a matter of fact, this patient has many findings inconsistent with the diagnosis of ALS. Those are particularly well demonstrated by the electrophysiologic abnormalities. In this case, there is evidence of a predominant motor peripheral neuropathy fulfilling criteria
and absent F-waves [3]. The mild sensory involvement is demonstrated by the difference in sural nerve amplitude and the findings of immunoglobulins at nodes of Ranvier in the surd nerve biopsy. The development of a progressive weakness after a rabies vaccine could suggest a diagnosis of a postinfectious polyradiculopathy, possibly with some degree of central involvement [4].While it may be intriguing to consider that a motor system degeneration may be caused by anti-GM1 antibodies binding at the nodes of Ranvier and possibly at other neuronal structures as well, we disagree with the diagnosis of ALS in this patient, for which there is little supportive evidence. Such a diagnosis will, we are sure, confuse many readers.
Department of Neurology CHU Vaudoi’, Lauxanne Switzerland
References 1. World Federation of Neurology Subcommittee on Motor Neuron Disease. El Escorial criteria for diagnosis of amyotrophic lateral sclerosis. Presented at the VIIth International Congress on Neuromuscular Diseases, Munich, Germany, September 16-22,
1990 2. Santoro M, Thomas FP, Fink ME, et al. IgM deposits at nodes of Ranvier in a patient with amyotrophic lateral sclerosis, anti-GM 1 antibodies and multifocal motor conductiun block. Ann Neurol 1990;28:373-377 3. Cornblath DR. Electrophysiology in Guillain-Barri. syndrome. Ann Neurol 199U;27(suppl):S17-S20 4. Hemachudha T, Phanaphak P, Johnson RT, et a]. Neurologic complication of Semple-type rabies vaccine: clinical and immunologic studies. Neurology 1387;37:550-556
Reply
Lewis P. Rowland, MD, Maria Santoro, MD, Dale J. Lange, MD, Arthur P. Hays, MD,” F. Thomas, MD, M. E. Fink, MD, N. Wadia, MD, and N. Latov, MD, PhD Drs Steck and Kuntzer raise important issues. Dr Rowland joins the authors in replying because he suggested using “ALS” in the title of our paper.
Diagnosis of ALS Clinical diagnosis [If is based on adult onset of progressive disability with signs of lower motor neuron dysfunction in all cases, sparing sensation. If only lower motor neurons are affected clinically, the term is progressive spinal muscular atrophy. The term “ALS” is reserved for patients who also have definite upper motor neuron signs. Active tendon reflexes in limbs with fasciculating, wasted muscles are “probable upper motor neuron signs.” There has never been a formal evaluation of the accuracy of the clinical diagnosis of ALS. The only way to prove the diagnosis is by postmortem examination; even that may not give unequivocal answers. From personal experience, the reliability of clinical diagnosis probably exceeds 95 96.
Annals of Neurology
Vol 30 No 2
August 1991 225
