Primary lateral sclerosis is a type of neuromuscular disease affecting the upper motor neuron function, resulting in impaired motor speech production, hyperreflexia, spasticity and paresis of voluntary muscles.
The initial presentation of primary lateral sclerosis is usually progressive spasticity and paresis of the voluntary muscles. At an early stage, the lower limbs are affected unilaterally while the later stage is marked by bilateral involvement. Affected patients will subsequently experience difficulty in walking due to stiffness and slowness of their legs. Eventually walking aids may be required.
Once the disorder progresses to involve the bulbar muscles, patients will present with dysphagia and dysarthria. In certain cases bulbar muscle dysfunction may occur as the initial presentation. Some patients display urine incontinence as a later symptom.
After onset, primary lateral sclerosis typically progresses slowly, but rapid advancement has also been noted. The course of disease may therefore be different from one patient to another.
This locus had not been implicated in ALS or in hereditary spastic parapareses, spinal muscular atrophy, or spinal and bulbar muscular atrophy.  A genetically mediated PLS look-alike, progressive familial paraparesis (hereditary spastic paraparesis [emedicine.com]
Atrophy (PMA)] experiencing muscle cramps. [mayo.edu]
deformities which are not present in PLS.4 The vast majority of patients present 20 years of age. [ncbi.nlm.nih.gov]
[…] y lat·er·al scle·ro·sis considered by many to be a subgroup of motor neuron disease; a slowly progressive degenerative disorder of the motor neurons of the cerebral cortex, resulting in widespread weakness on an upper motor neuron basis; spasticity, hyperreflexia [medical-dictionary.thefreedictionary.com]
[…] lateral sclerosis Disease definition Primary lateral sclerosis (PLS) is an idiopathic non-familial motor neuron disease characterized by slowly progressive upper motor neuron dysfunction leading to spasticity, mild weakness in voluntary muscle movement, hyperreflexia [orpha.net]
Spasticity with hyperreflexia, exaggerated jaw jerk and extensor plantar responses were eventually seen in all patients. Anterior horn cell involvement developed in three cases. [ncbi.nlm.nih.gov]
Codes ICD10CM: G12.29 – Other motor neuron disease SNOMEDCT: 81211007 – Primary lateral sclerosis Differential Diagnosis & Pitfalls Amyotrophic lateral sclerosis Spinal muscular atrophy Hereditary spastic paraplegia Cervical myelopathy Transverse myelitis [visualdx.com]
Ever since, long-standing sceptical discussion has arisen from the observation that many patients with PLS seemed ultimately to have different diseases such as ALS, spinal multiple sclerosis, or cervical spondylotic myelopathy. [oxfordmedicine.com]
Three patients were diagnosed as PLS, but seven were at first misdiagnosed: three as ALS, two as multiple sclerosis, one as Parkinson's disease, and one as cervical compression myelopathy. [jnnp.bmj.com]
Radiation-induced myelopathy Type 1 Excludes myelopathy NOS ( G95.9 ) paralysis G12.20 ICD-10-CM Diagnosis Code G12.20 Motor neuron disease, unspecified 2016 2017 2018 2019 Billable/Specific Code meaning progressive muscular atrophy G12.21 Duchenne-Aran [icd10data.com]
Multiple Sclerosis (MS) Completed NCT00573443 Phase 3 dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg;dextromethorphan hydrobromide 30 mg and quinidine sulfate 10 mg;Placebo 41 Efficacy of Riluzole in Patients With Cervical Spondylotic Myelopathy [malacards.org]
Examination revealed upper motor neuron findings of pseudobulbar palsy and spastic quadriplegia, without dementia, cerebellar, extrapyramidal or sensory signs. [ncbi.nlm.nih.gov]
During the second year of life, they lose the ability to walk (some patients never walk due to early severe spasticity) and then develop slowly progressive upper motor neuron disorders including pseudobulbar palsy and spastic quadriplegia. [orpha.net]
In conclusion, these cases represent a subgroup of PLS patients in whom pyramidal slowness may be mistaken for akinesia, and spasticity misconstrued as rigidity, leading to an erroneous diagnosis of atypical parkinsonism. [ncbi.nlm.nih.gov]
We encountered three patients with primary lateral sclerosis (PLS) showing bradykinesia, frozen gait, and severe postural instability, as well as slowly progressive spinobulbar spasticity. [ncbi.nlm.nih.gov]
The diagnosis of primary lateral sclerosis can be obtained clinically especially if it is first encountered as a late presentation. Diagnostic workup is necessary in ruling out possible differentials since the majority of motor neuron diseases present in a similar way. Laboratory investigations include assessment of cerebrospinal fluid from lumbar punctures to check for infection, genetic studies to rule out familial neuropathies, urine analysis to evaluate heavy metal poisoning and blood work to exclude other infections and metabolic derangement .
Imaging workup involves carrying out nerve conduction studies. Slow impulses are characteristic in the late stages of motor neuron diseases. Electromyography is necessary to differentiate between muscle and nerve diseases. Magnetic resonance imaging (MRI) of the brain and spinal cord may also be conducted as adjuncts to rule out possible differential diagnoses .
Treatment for PLS is mainly supportive; definitive measures are yet to be identified. Spasticity being the major symptom is treated with baclofen and tizanidine. The benzodiazepine group of drugs such as diazepam and clonazepam can also be used to remedy spasticity . Analgesics are prescribed to manage pain arising from spasticity. In certain patients, antidepressants are administered for PLS related depression.
Other supportive measures
- Physical therapy involves stretch exercises that enhance the range of motion of the joints. This serves to prevent the development of contractures resulting from spasticity. The exercises can be carried out at home by the primary caregiver .
- Non invasive ventilatory support may be required in patients who suffer from respiratory failure which may occur late in the course of the disease.
- Symptomatic relief can be achieved by use of massage or pool therapy.
- Occupational therapy may be necessary for patients who develop certain disabilities.
Primary lateral sclerosis has a gradual progression that manifests as insidious development of motor neuron dysfunction and muscle disability. It has no adverse implication on life expectancy but according to statistics from a study on 36 patients with PLS, the disease was linked to an estimated median survival period of 20 years .
Adult PLS is considered idiopathic and non-familial.
Juvenile PLS is an autosomal recessive disorder whose exact etiological mechanism is unknown. However, the characteristic motor neuron dysfunction seen in this condition is attributed to mutations in the ALS2 gene responsible for coding of protein alsin, present in these neurons. Of note is the absence of these gene mutations in adult PLS .
The adult form is more common than the juvenile form. In terms of distribution, PLS shows an age predilection of 40-60 years and a higher male to female ratio.
In a sharp contrast against related conditions like amyotrophic lateral sclerosis, statistics on PLS is not well documented and most of the data available has been inferred from studies on ALS. There is documentation of a PLS incidence rate of 0.01 cases per population of 100,000 . This was generated from reports of 8 patients with PLS, identified from a group of 500 patients with ALS within a 10 year period margin. A PLS prevalence rate of 2 million was then inferred from the ALS patient data that consisted of a population of 4 million . These statistics match data from a conservative estimate which showed that the number of people living with PLS in the United States is below 500. The exactness of these figures is however difficult to prove.
Adult primary lateral sclerosis is considered non-hereditary. An unique autosomal dominant variant of adult PLS was identified in a French-Canadian family, mapping to 4ptel, a gene on chromosome 4p16.1. Similar disorders like ALS, hereditary spastic paraparesis and spinal/bulbar muscular atrophy have also been linked to the locus 4p16.1. .
The juvenile form of primary lateral sclerosis occurs rarely and has been mapped to ALS2, a gene on chromosome 2q33.2. This is often the result of a single missense mutation and at least ten deletion mutations of ALS2. ALS2 encodes protein alsin which is important for motor nerve function. Alsin is a guanine nucleotide exchange factor responsible for cell signalling and protein trafficking functions by regulating activity of the Ras superfamily of GTPases .
Preventive measures for primary lateral sclerosis are yet to be discovered.
Primary lateral sclerosis (PLS) is a rare condition in the category of motor neuron diseases . It primarily targets facial, upper limb and lower limb corticospinal neurons  and its etiological basis is progressive degeneration of neurons in the motor cortex. PLS targets neurons in an ascending manner; beginning with the muscles of the legs, trunk, upper limbs and finally affecting the bulbar muscles which are responsible for the functions of speech, chewing and swallowing. Clinically, it presents with slowly progressive features of paresis, spasticity, slow movement, impaired speech and abnormalities of balance. PLS is more common in men than women and occurs between the ages of 40 and 60 years. In terms of prognosis, PLS is slowly progressive with the disease course encompassing several years and sometimes decades. Commonly, PLS presents in a similar manner as spastic paraplegia or amyotrophic lateral sclerosis (ALS). It therefore requires thorough diagnostic investigations to rule out these differentials.
Primary lateral sclerosis (PLS) is a disease primarily affecting nerves and muscles. It occurs when upper motor neurons (nerve cells transmitting impulses from the brain) undergo progressive degenerative changes that reduce their functionality. As a result, transmission of impulses to voluntary muscles is slowed down, impairing their strength and function.
The cause of adult onset PLS remains unknown and such cases tend to occur randomly. However, when the disease occurs in children, it is linked to hereditary causes such as gene mutations that affect the nerve function.
Symptoms vary from one person to another and usually resemble other diseases that affect nerves and muscles. Consultation with a clinician may be necessary. Symptoms may include:
- Muscle weakness and spasms beginning in the legs and progressing to the trunk, arms and eventually the face
- Difficulty in walking and maintaining balance
- Clumsiness of legs and hands
Advanced disease may present with the following:
A diagnosis of PLS can be achieved from relevant medical history and proper physical examination. It is necessary to carry out investigative tests to rule out other possible disorders which may present in a similar manner.
- Laboratory assessments include blood tests, urine analysis, cerebrospinal fluid analysis and genetic studies. These are used to rule out infections, heavy metal poisoning and other genetic causes.
- Imaging studies include magnetic resonance imaging of the brain and spinal cord, nerve conduction studies and electromyography studies. These tests assess the nerve function.
Treatment for primary lateral sclerosis is mainly supportive and aims at the alleviation of symptoms. Spasticity of muscles is treated with baclofen and tizanidine. Other drugs such as diazepam and clonazepam may also be administered. Other treatment options include physical and occupational therapy to relieve spasms and prevent the loss of muscle and joint function.
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