Spinal Onset Juvenile Amyotrophic Lateral Sclerosis in a 16-Year-Old Girl: A Rare Case Report

Abstract

Introduction:

Juvenile amyotrophic lateral sclerosis (J-ALS) is extremely rare neurodegenerative motor neuron disorder that begins in early childhood or adolescence, before the age of 25 years old. It is characterized by gradual disease progression with comparison to adult-onset ALS and is often linked to genetic mutations.

Case Presentation:

A 16-years-old female presented with long history of generalized weakness since age of 10 years, followed by bilateral sensorineural hearing loss, bulbar symptoms, and limb spasticity. Neurological examination revealed upper motor neuron signs in upper limbs, lower motor neuron signs in lower limbs, and bulbar involvement. Nerve conduction test was normal however, MRI showed early degenerative changes, and diagnosed with J-ALS after careful evaluation. She was started on Riluzole. Despite ICU care and supportive interventions including PEG and tracheostomy, she succumbed to respiratory failure.

Discussion:

Rarity, atypical presentation, and finical constraints can delay diagnosis of J-ALS. However, early diagnosis after careful evaluation of clinical symptoms, medical history, electrophysiological and imaging studies followed by prompt treatment with Riluzole and supportive interventions can help prolong survival and improve quality of life.

Conclusion:

J-ALS is a rare motor neuron disease which possess immense diagnostic challenges, can exhibit relentless progression over short period of time with time.

Introduction

Juvenile amyotrophic lateral sclerosis (J-ALS) is a rare neurodegenerative disorder causing degeneration of upper motor neurons and lower motor neurons and typically defined as onset before the age of 25 years. A rare study conducted across 46 specialized ALS centers in Europe found that the prevalence of ALS cases starting before age 18 years is about 0.008 per 100 000 people. This represents less than 0.1% of all ALS cases^[1]. J-ALS is associated with considerable disability in the affected young and early death in some forms of the disease^[2]. Whereas, the prevalence of ALS is 5/100 000 population and the incidence is 2–3 cases/100 000 population per year worldwide^[3]. The traditional view of ALS as a purely motor disease, emphasizes the absence of sensory symptoms and normal sensory neurography^[4]. Sensory or autonomic disturbances are often overshadowed by severe motor symptoms and considered atypical for ALS^[5].

HIGHLIGHTS

• Juvenile ALS is an uncommon, with mean survival of 2–5 years, yet our patient lived over 15 years.

• It can present with atypical features like sensorineural hearing loss and early spinal onset.

• Early bulbar and respiratory involvement worsen prognosis, requiring timely interventions like PEG and ventilatory support.

• Management remains supportive, with Riluzole offering limited benefit in slowing disease progression.

The case report is written in accordance with the SCARE guideline 2025^[6].

Case presentation

A 16-year-old unmarried female who was born from non-consanguineous marriage, presented to our OPD with generalized body weakness since 10 years of age, hearing loss for 2 years, slurring of speech for 1 year, and difficulty in swallowing for 3 months. Weakness started from right foot then gradually progressed to right arm, left leg, and left arm. She was unable to perform her household activities, had to take rest multiple times on the way to school. Then, it gradually progressed over the years and had difficulty in standing from sitting position without support. It was associated with wasting of lower limbs. She felt sensation of heaviness, stiffness in upper limbs. Right before this illness, she had no history of trauma, infections or any vaccinations. She reported a gradual decline of her hearing over 2 years without accompanying symptoms like tinnitus, dizziness, and vertigo. In addition, she experienced difficulty with speech since last 1 year. She has trouble in swallowing both liquid and solid food since last 3 months but she doesn’t give history of regurgitation, cough on swallowing, constipation, bowel dysfunction, dementia, shortness of breath, ataxia, and seizure.

On presentation to our OPD, vitals were stable. Patient was alert, conscious (GCS 15/15), oriented to time, place, and person. Cranial nerve examinations were intact except for CN VIII (decreased hearing on B/L ear), CN IX & X (dysarthria, slurring of speech, dysphagia), and CN XII (tongue atrophy present). Motor examination shows decreased bulk, power, tone and reflexes in bilateral lower limbs whereas, there was increased tone and reflexes in upper limb. Power was 3/5 in lower limbs and 4/5 in upper limbs. Clonus was present bilaterally. Plantar reflex was mute and superficial abdominal reflex was absent. Sensory and cerebellar examination were intact.

After admission, blood investigations, vitamin-B12, TPHA, VDRL, copper, TFT, PTH, CRP, ESR, riboflavin level were sent and found to be normal (Table 1).

Table 1.

Laboratory investigations

Test	Result	Reference range
Free tri-iodothyronine (fT3)	4.31 pmol/L	(3.1–6.7 pmol/L)
Free thyroxine (fT4)	13.67 pmol/L	(12–22 pmol/L)
Thyroid stimulating hormone (TSH)	3.39 µIU/ml	(0.5–5.0 µIU/ml)
Parathyroid Hormone (PTH)	41 pg/ml	10–65 pg/ml
B12	560 pg/ml	187–833 pg/ml
B2	4 µg/L	1–19 µg/L
Copper	72	62–140 µg/dL
C-reactive protein (CRP)	2 mg/l	< 10 mg/L
Erythrocyte sedimentation rate (ESR)	4 mm/h	0–20 mm/h
Venereal Disease Research Laboratory (VDRL)	Non-reactive
White blood cells (WBC)	7900 /cmm	4000–11 000/cmm
Hemoglobin (Hb)	16.1 g/L	13.5–18 g/L
Red blood cels (RBC)	5.48 million/cumm	4.5–5.5 million/cumm
Neutrophils	59.7%	46–75%
Lymphocytes	33.6%	22–45%
Monocytes	3.6%	2–10%
Eosinophils	3.1%	1–6%
Basophils	0.0%	0–1%
Packed cells volume (PCV)	46.6%	36–54%

MRI brain and spinal cord showed normal findings in T1 and T2 FLAIR sequence whereas early degenerative changes were seen in T2 weighted sequence. (Figure 1,2,3,4 and 5) Nerve conduction test was also normal. ENT Consultation was also done and Pure tone audiometry showed sensorineural hearing loss. Patient has been using Riluzole 50 mg 12 hourly for last 2 years which was prescribed from our center. This time, after a few days of admission, she needed intensive care unit (ICU) for aspiration pneumonitis, as disease progressed to bulbar palsy, leading to sudden drop in her oxygen saturation up to 70% along with weak respiratory effort. Patient needed intubation and ventilation. After addressing her medical issues, she was discharged on 30th day of admission due to her parent’s decision to leave against medical advice, driven by financial constraints. Prior to discharge from hospital, she had percutaneous endoscopic gastrostomy (PEG) tube and tracheostomy tube placed and she was put on a portable bilevel positive airway pressure (Bi-PAP) ventilator. Our patient was advised to continue Riluzole 50 mg 12 hourly and her family was properly educated and counseled about the disease. Patient and patient party was advised to make lifestyle adjustment and to follow-up regularly. After 7th day of discharge, she died of respiratory failure.

Figure 1.

MRI of brain (A. Sagittal section. Axial section) T1-weighted sequence showing no apparent abnormalities.

Figure 2.

MRI: (A) Brain (Axial plane), (B) spinal cord (Sagittal plane), T2-weighted sequence showing normal finding in brain and early degenerative changes in spine.

Figure 3.

MRI brain, T2 FLAIR (Axial plane) showing normal morphology and normal parenchymal signal intensity.

Figure 4.

MRI Brain, T2-weighted sequence (Coronal plane) showing normal morphology of brain.

Figure 5.

MRI of spinal cord, T2-weighted sequence in sagittal plane showing normal morphology and signal intensity.

Discussion

J-ALS is a rare, progressive neurodegenerative disease that primarily targets motor neurons, leading to muscle weakness and paralysis that typically begins before 25-years of age. It is a sequence of events leading to programmed death of specific group of neuron^[7]. J-ALS has many variants like spinal onset, bulbar onset and respiratory onset^[8]. About 40% case are linked to specific genetic mutations^[2]. FUS, SETX, ALS2, SPG11, SOD1, SPTLC1, UBQNL2, SIGMAR1, and other several genes are commonly linked. However, C9orf72 gene mutation is frequently inherited gene in adult onset ALS^[9].

In our case, 16-years-old female, initially exhibited spinal onset symptoms manifesting limb weakness, wasting of limbs that gradually progressed to involve bulbar region, resulting slurred speech, and swallowing difficulties. Additionally, she had sensorineural hearing loss. This is quite unusual from classical cases. This is very rare type of ALS, Juvenile-ALS. The mean survival age for ALS patients is 2–5 years, but this patient has lived beyond that. spinal muscular atrophy (SMA), hereditary spastic paraplegia (HSP), multifocal motor neuropathy (MMN) Charcot–Maries–Tooth (CMT) disease, primary lateral sclerosis (PLS), juvenile Parkinsonism, and Wilson disease. SMA, HSP, PLS CMT, and MMN were ruled out because of simultaneous presence of UMN and LMN signs. Juvenile-Parkinsonism was ruled out because of absence of tremor, bradykinesia, and rigidity. Wilson disease was ruled out given the absence of movement disorder such as tremors, dystonia as well as the presence of normal liver function test and a normal serum ceruloplasmin.

J-ALS risk factors involve a blend of genetic predispositions and environmental exposure, though their exact relationships are not fully understood. Viral effects, exotoxins, increased oxidative stress, mitochondrial dysfunction, impaired DNA repair mechanism and chronic inflammation are suspected to be the causes of ALS but not proven yet^[7,10]. There are more than 20 gene mutations found that are known to cause ALS. The major gene is the C9ORF72 gene, responsible for 30–50% of familial ALS and 7% of sporadic ALS^[11]. Due to the patient’s limited resources, we were unable to perform gene analysis in this case.

The rarity of disease and diversity of symptoms, often mimicking other conditions, has created major challenges in diagnosing J-ALS. J-ALS is a diagnosis of exclusion. Diagnosis of ALS relies on three basic principles: identifying symptoms of functional impairment in specific body regions, detecting signs of both peripheral and central motor neuron disease and progression of these impairments over time^[12]. Electromyography and nerve conduction tests aid in diagnosis of ALS. New criteria and awareness of disease types can speed-up diagnosis, while improved prognosis models and novel tools like biomarkers and imaging can help track disease progression and inform patient care and planning^[13]. Previously, MRI was limited to rule of ALS mimicker like radiculo-myelopathy and lumbosacral radiculopathy but now-a-days, it is used to assess the subclinical UMN involvement and detecting cerebral motor and extra-motor neuron degeneration^[14]. In our case, patient was diagnosed with ALS after careful evaluation of symptoms, medical history, and nerve conduction test along with diagnostic imaging, to rule out other possible conditions.

Currently, there is no specific cure for this disease. ALS treatments, like Riluzole and Edaravone, offer limited survival benefits, and many proposed therapies are not in late-phase trials. Future progress is expected from advances in genetics and novel approaches, such as gene therapy and stem cell treatments, which may potentially modify the disease course^[15]. The purpose of the presentation is to highlight one more pattern of young onset ALS, a variety of motor neuron disease.

Conclusion

J-ALS is an extremely rare but life threatening disease of unknown cause. Rarity of disease and complexity of clinical presentation poses major setback in the diagnosis. However, early diagnosis and effective treatment aimed at providing aggressive symptoms relief and preventing complication can improve and extend quality of life.

Ethical approval

This case report did not intervene with the patient’s treatment plans and hence it did not require ethical approval.

Consent

Written informed consent was obtained from the patient’s parents/legal guardian for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Sources of funding

Not applicable.

Author contribution

B.B.: Writing, Original draft preparation, Editing; A.C.: Editing and Study Concept; D.A.: Writing and original draft preparation; S.B.: Editing of original draft; D.P.: Manuscript reviewer and supervisor Rajan Budha: Editing of orginal draft; S.A.: Writing orginal draft; R.K.G.: Manuscript reviewer and supervisor. All authors have read and agreed to the final version of the manuscript.

Conflict of interst

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Guarantor

Dr. Bishal Budha

Email: bishalbc265@gmail.com

ORCID: 0009-0001-5276-3494

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1. Name of the registry: None

2. Unique Identifying number or registration ID: None

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Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.