Case Report
1 Master's Program in Neurology - University of Vassouras and School of Medicine - University Iguaçu - RJ, Brazil
2 Iguaçu University - UNIG - Department of Neurology of Hospital Geral de Nova Iguaçu - RJ, Brazil
3 Department of Neurology of Federal University of Rio de Janeiro - UFRJ, Brazil
4 Department of Medicine - UNIFESP - Paulista School of Medicine, Brazil
Address correspondence to:
Antônio Marcos da Silva Catharino
Rua Gavião Peixoto 70, Room 811, CEP 24.2230-100, Icaraí, Niterói, RJ,
Brazil
Message to Corresponding Author
Article ID: 101340Z01MO2022
Introduction: Amyotrophic lateral sclerosis (ALS), also called motor neuron disease (MND), is a progressive, neurodegenerative, and inexorable disease that affects the neurons of the anterior horn of the spinal cord, as well as the lateral funiculus. A rare variant of ALS was first described in 1918 by Patrikios and Marie, called the pseudopolyneuritic form or Marie-Patrikios disease. It is characterized by an initial manifestation with melting of the feet, distal weakness of the muscles of the anterior compartment of the leg, and absence of the Achilles tendon reflex. We present an atypical case of ALS, marked by polyneuropathy and involvement of upper and lower motor neurons.
Case Report: A 70-year-old man reported that approximately four years ago he started having pain in the thoracic region with subsequent paresis in the lower limbs. Initially, compressive myelopathy, transverse myelitis, and spastic paraparesis of various causes were thought to be the cause. However, the non-impairment of the superficial and deep sensibility, obviously, with absence of sensorial level, associated to the absence of specific imaging findings in the thoracic and lumbar spine, a normal complete laboratory, ruled out such hypotheses.
Conclusion: We highlight that the pseudopolyneuritic form presented in this study has a better prognosis and survival rate when compared to other subtypes of ALS. Thus, a detailed investigation including physical, neurological, and electrophysiological examination is essential to establish the diagnosis and increase the scarce knowledge about this condition.
Keywords: Achilles tendon reflex, Amyotrophic lateral sclerosis, Heterogeneity, Pseudopolyneuritic form
Amyotrophic lateral sclerosis (ALS), also called motor neuron disease (MND), is a progressive, neurodegenerative, and relapsing disease which affects the neurons of the anterior end of the spinal cord, as well as the lateral funiculus [1]. The incidence in the population is heterogeneous and ranges from 0.73 to 1.89 cases per 100,000 persons per year in South Asia and Northern Europe, respectively [2],[3]. It is a progressive condition comprising degeneration of the motor system at various levels: bulbar, cervical, thoracic, and lumbar [4].
A rare variant of ALS was first described in 1918 by Patrikios and Marie, called the pseudopolyneuritic form or Marie-Patrikios disease. It is characterized by an initial manifestation with melting of the feet, distal weakness of the muscles of the anterior compartment of the leg, and absence of the Achilles tendon reflex, mimicking a peripheral neuropathy. Patellar and upper limb tendon reflexes may show hyperreflexia [5].
This form may be confused with some clinical conditions, such as lumbar plexopathy, fibular neuropathy, and distal myopathy, due to the presence of foot melting. Therefore, the patient’s clinical history, neurological examination, and electrophysiological evaluation should be carefully analyzed for a differential diagnosis [6].
Other syndromes related to this spectrum of ALS disorders include progressive bulbar palsy, progressive spinal amyotrophy, primary lateral sclerosis, unstable arm syndrome, and unstable leg syndrome—pseudopolyneuritic form of ALS [7].
Symptoms related to upper limb and bulbar involvement are minimal or even nonexistent, although they invariably occur in advanced stages of the disease. Furthermore, it is difficult to distinguish in early stages from other disorders such as distal spinal atrophy, lumbosacral radiculopathy, and multifocal motor neuropathy [8].
Histopathologically, a cellular degeneration had been described preferentially of the lumbar spinal cord. Later, severe loss of lower motor neurons throughout the spinal cord and depletion of the minimal neurons in the middle zone of the anterior horn of the lumbar spinal cord were described. However, to date, knowledge about the clinical and histopathological findings of the variant is limited [9].
Therefore, the aim of the present study is to demonstrate, through a case report, a rare form of ALS, the pseudopolyneuritic or Marie-Patrikios form, and thus, to discuss the current knowledge about the clinical and histopathological findings of the variant.
A 70-year-old man reported that approximately four years ago he started having pain in the thoracic region with subsequent paresis in the lower limbs. Initially, compressive myelopathy, transverse myelitis, and spastic paraparesis of various causes were thought to be the cause. However, the non-impairment of the superficial and deep sensibility, obviously, with absence of sensorial level, associated to the absence of specific imaging findings in the thoracic and lumbar spine, a normal complete laboratory (Vitamin B12, HTLV, genetics for spastic paraparesis, among marked inflammatory, infectious, and immunological) and normal cerebrospinal fluid, ruled out such hypotheses. It is worth mentioning that the electroneuromyography identified a sensorimotor polyneuropathy with axonal predominance. Neurological examination revealed amyotrophy and paresis [Medical Research Council (MRC): grade 3/4] in the lower limbs, with Babinski's sign bilaterally present, and mild spasticity (Ashworth 1) in the evaluated groupings (quadriceps, gastrocnemius, soleus, and posterior tibial), as well as in the finger flexors. No myofasciculations were observed. In the upper limbs only hyperreflexia with Hoffman’s sign present on the right. Muscle strength and sensitivity were normal. After six months, the patient returns for a medical consultation with complaints related to the progression of muscle weakness, confining him to a wheelchair; (MRC: 1/2) in the muscles of the lower limbs. At this point muscle weakness had already started to affect the upper limbs (MRC: 3/4) (Figure 1); being associated with myofasciculations. His cranial nerves were normal with normal cognition and higher functions. Upon further electroneuromyography examination, a neurogenic pattern with fibrillation potentials, positive waves, and myofasciculations was demonstrated. Added to this was a predominance of neurogenic (long duration, polyphasic, and large amplitude) motor unit action potentials (MUAPs). Findings of compatibility to sensorimotor polyneuroradiculopathy and plexopathy, more pronounced in the lower limbs, with acute and chronic denervation were also described. With disease progression and new findings of first and second motor neuron involvement, the patient was diagnosed with ALS pseudopolyneuritic form of Marie-Patrikios; an association between polyneuroradiculopathy and motor neuron disease.
Unfortunately, the patient has been showing rapid evolution, already with damage in the four limbs and breathing. Dysphagia is already present on some occasions, mainly with liquids.
Amyotrophic lateral sclerosis is a prototype of motor neuron disease and numerous theories have been proposed for its etiopathogenesis, but none so far have been unifying, among them: genetic factors, excitotoxicity, oxidative stress, mutations in the copper-zinc SOD1 gene, mitochondrial dysfunction, neurofilament, protein aggregation, etc. The average age of disease onset varies between 55 and 65 years, and men are more affected compared to women, with a ratio of 1.5:1, respectively [10].
The pseudopolyneuritic form of ALS (Table 1) is a subtype characterized by distal weakness of the lower limbs and absence of the Achilles tendon reflex. The etiopathogenesis of the Patrikios form is defined by the loss of myelinated fibers in the corticospinal tract of the thoracic and lumbar spinal cord segments [11].
This variant was discovered by Pierre Marie and first described by Patrikios, thus named the Marie-Patrikios form. It was described as a syndrome which includes weakness of distal onset in the lower limbs, clinically asymmetric, with absence of tendon reflexes in the lower limbs, slow progression, and late manifestations of the upper motor neuron. Moreover, this subtype occurs preferentially in women when compared to other forms of ALS [12].
Studies indicate that this form has a significantly better prognosis compared to the bulbar form of ALS. The survival time with this form is the onset of symptoms ranges from 30 to 69 months, and the frequency is 1–17.5% [13].
The recognition of this form of ALS is essential for clinicians, since the combination of distal lower limb weakness, in addition to the absence of the Achilles reflex, often suggests a peripheral neuropathy. In clinical practice, the identification of hyperreflexia in the patellar and/or upper limb reflexes may be the key to the diagnosis of ALS, even if in exceptional cases no signs of upper motor neuron involvement are observed [14].
We highlight that the pseudopolyneuritic form presented in this study has a better prognosis and survival rate when compared to other subtypes of ALS. In this regard, due to its symptomatological particularities, there may be a misunderstanding regarding the differential diagnosis of polyneuropathy. Thus, a detailed investigation including physical, neurological, and electrophysiological examination is essential to establish the diagnosis and to increase the scarce knowledge about this condition. The polyneuritic form of Patrikios is in the hall of variants of the classic ALS. Differential diagnosis is based on physical and electrophysiological examination. The prognosis, although considered by some authors as less aggressive, does not seem to us to be different from the classic cases of ALS.
1.
Marin B, Boumédiene F, Logroscino G, et al. Variation in worldwide incidence of amyotrophic lateral sclerosis: A meta-analysis. Int J Epidemiol 2017;46(1):57–74. [CrossRef] [Pubmed]
2.
Chancellor AM, Warlow CP. Adult onset motor neuron disease: Worldwide mortality, incidence and distribution since 1950. J Neurol Neurosurg Psychiatry 1992;55(12):1106–15. [CrossRef] [Pubmed]
3.
Cronin S, Hardiman O, Traynor BJ. Ethnic variation in the incidence of ALS: A systematic review. Neurology 2007;68(13):1002–7. [CrossRef] [Pubmed]
4.
Mitchell JD, Borasio GD. Amyotrophic lateral sclerosis. Lancet 2007;369(9578):2031–41. [CrossRef] [Pubmed]
5.
Cappellari A, Ciammola A, Silani V. The pseudopolyneuritic form of amyotrophic lateral sclerosis (Patrikios’ disease). Electromyogr Clin Neurophysiol 2008;48(2):75–81. [Pubmed]
6.
Koc F, Yerdelen D. Motor neuron disease and its association with non-Hodgkin’s lymphoma. Neurosciences (Riyadh) 2008;13(4):458–9. [Pubmed]
7.
Nalini A, Thennarasu K, Gourie-Devi M, Shenoy S, Kulshreshtha D. Clinical characteristics and survival pattern of 1,153 patients with amyotrophic lateral sclerosis: Experience over 30 years from India. J Neurol Sci 2008;272(1–2):60–70. [CrossRef] [Pubmed]
8.
O'Reilly DF, Brazis PW, Rubino FA. The misdiagnosis of unilateral presentations of amyotrophic lateral sclerosis. Muscle & Nerve 1982;5(9):724–26. [CrossRef]
9.
10.
Wijesekera LC, Leigh PN. Amyotrophic lateral sclerosis. Orphanet J Rare Dis 2009;4:3. [CrossRef] [Pubmed]
11.
Wijesekera LC, Mathers S, Talman P, et al. Natural history and clinical features of the flail arm and flail leg ALS variants. Neurology 2009;72(12):1087–94. [CrossRef] [Pubmed]
12.
Hemmer R. On the peroneal form of amyotrophic lateral sclerosis. [Article in German]. Nervenarzt 1955;26(9):400–1. [Pubmed]
13.
Mortara P, Bardelli D, Leone M, Schiffer D. Prognosis and clinical varieties of ALS disease. Ital J Neurol Sci 1981;2(3):237–42. [CrossRef] [Pubmed]
14.
Kobayashi Z, Tsuchiya K, Arai T, et al. Pseudopolyneuritic form of ALS revisited: Clinical and pathological heterogeneity. Neuropathology 2010;30(3):372–80. [CrossRef] [Pubmed]
Marco Orsini - Conception of the work, Design of the work, Acquisition of data, Drafting the work, Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Antônio Marcos da Silva Catharino - Analysis of data, Revising the work critically for important intellectual content, Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Valéria Camargo Silveira - Analysis of data, Revising the work critically for important intellectual content, Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Carlos Henrique Melo Reis - Analysis of data, Revising the work critically for important intellectual content, Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Marcos RG de Freitas - Conception of the work, Design of the work, Analysis of data, Revising the work critically for important intellectual content, Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Acary Bulle de Oliveira - Acquisition of data, Analysis of data, Revising the work critically for important intellectual content, Final approval of the version to be published, Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Guarantor of SubmissionThe corresponding author is the guarantor of submission.
Source of SupportNone
Consent StatementWritten informed consent was obtained from the patient for publication of this article.
Data AvailabilityAll relevant data are within the paper and its Supporting Information files.
Conflict of InterestAuthors declare no conflict of interest.
Copyright© 2022 Marco Orsini et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.