Case of a 59 year old female with ALS

 

Case Description

A 59-year-old female , company employee, presented with bilateral upper and lower limb weakness for 6 months.

The weakness initially began in her left lower limb, it was insidious in onset and progressive in nature. She experienced frequent falls while carrying out her daily activities and experienced multiple injuries on her lower limbs.

Gradually, she developed weakness in the left upper limb.

She was able to carry out her daily activities with discomfort for 4 to 5 months, after which the weakness spread bilaterally to her right upper and lower limb.

She was unable to maintain her balance or walk without support and required assistance to bathe or use the washroom. The patient was unable to raise her lower limbs from the bed in supine position and complained of neck pain radiating bilaterally to her upper limbs.

On examination, the bulk and power of the muscles were reduced and deep tendon reflexes were exaggerated bilaterally in both upper and lower limbs.

There were no deficits in her cognition or memory, no dysarthria or loss of sensations, and her bowel and bladder movements were normal.

Her Laboratory investigations revealed raised ESR (25mm/hr) and mild normocytic, normochromic anaemia. Liver function tests, Renal function tests, Thyroid profile and Vitamin D estimations were within normal ranges.

MRI of the cervical spine revealed

- Mild posterior central and bilateral subarticular disc protrusions at C5-C6 levels, indenting the anterior subarachnoid space, spinal cords and bilateral exciting nerve roots.

- Mild Posterior central disc bulge at C3, C4 Level without significant nerve root compression.

-Spinal Canal narrowing at C5-C6 and C6 -C7 levels due to disc protrusions and flaval ligament thickening.

EMG study revealed decreased motor unit recruitment with low amplitude polyphasic MUAP and abnormal spontaneous activity–fasciculation potentials.

Nerve conduction velocity study suggested axonopathy and demyelinating early polyneuropathy.

In the Motor Conduction Study there was wide and low amplitude CMAP present in bilateral Median, Ulnar, Common Peroneal and Tibial nerves with normal conduction velocities and normal F wave latency.

The Sensory conduction study done on the bilateral median, ulnar and sural nerves revealed normal conduction velocity and normal amplitude SNAP.
Thus, the patient was diagnosed with Amyotrophic Lateral Sclerosis and was started on the tablet riluzole 50 mg twice a day and vitamin E supplementation.

 

 

Discussion

A middle-aged woman with amyotrophic lateral sclerosis.

This case depicts the clinical proregression of the disease, motor manifestations and the transition from independent movement to functional limitation in a patient with ALS.

The patient was diagnosed with Amyotrophic Lateral Sclerosis, which is also known as “Lou Gehrig’s disease” [1]. It is a fatal neurodegenerative disorder of upper and lower motor neurons characterised by focal onset muscle weakness and rapid disease progression.[2]

Incidence rates of ALS all over the world range between 0.6 to 3.8 per 100000 person-years [3], while in India the frequency of new cases is 5 in 10000[4].

Even though ALS is a comparatively rare disease, the mortality rates are high. Approximately 50% of people diagnosed with ALS live at least three or more years after diagnosis. About 25% live five years or more and up to 10% live more than 10 years [5]. Hence it is the need of the hour to develop, better therapeutics and rehabilitation treatments.

According to modelling studies, ALS involves interactions between molecular and genetic factors, which lead to reduced uptake of glutamate (due to dysfunction of excitatory amino acid transporter 2).

Mutations in the superoxide dismutase-1 (SOD-1) gene cause the accumulation of intracellular aggregates and defective axonal transport. [2]

There also is activation of microglia, which results in the secretion of proinflammatory cytokines and subsequent neurotoxicity. [2]

Death of the peripheral motor neurons in the spinal cord and brainstem leads to denervation and atrophy of corresponding muscle fibres and the loss of fibres in the lateral columns, the resulting fibrillary gliosis imparts a particular firmness. [6]

Learning Outcomes

Characteristic signs

ALS typically presents with progressive muscle weakness having a focal onset, associated with muscle atrophy, fasciculations, muscle cramps, slowness of movements and muscle stiffness.

In Spinal ALS (seen in two-thirds of the patients) the presentation involves unilateral distal muscle weakness and atrophy of upper or lower limbs. While in Bulbar ALS (seen in one-third of patients) the presentation involves dysarthria or dysphagia. In one-third of the patients, there is presence of exaggerated emotions which is referred to as the pseudobulbar effect.

On clinical examination, Signs of

Lower Motor Neuron involvement includes muscle weakness, atrophy, fasciculations and reduced muscle tone, while Signs of UMN include hyperreflexia, increased muscle tone and slowness of movements. [7]


IN OUR PATIENT

The patient presented with Spinal ALS (as there was absence of dysphagia, dysarthria and exaggerated emotions).

The disease progression and transition independent movement to dependence for movement, is depicted in figure 1.

Signs of lower motor neuron involvement included – muscle weakness, atrophy and reduced muscle tone, while signs of upper motor neuron involvement included – hyperreflexia.Investigations

MRI of the cervical spine

MRI of the cervical spine is usually done to exclude ALS Mimic syndromes which are a heterogeneous group of conditions whose presentation and clinical features may resemble those of ALS at the beginning.[9]

In Autopsies conducted in patients with ALS, 47 per cent of individuals depict degeneration of the corticospinal tract, but the demonstrations of these abnormalities are limited on conventional MRI [11].

In a study aimed at investigating spinal cord conditions of ALS patients, revealed a higher incidence of cervical cord compression with 53.2 per cent of patients depicting cervical cord compression and 38.3 per cent of ALS patients with cervical spondylosis [10].

The Spinal cord in our patient was normal in thickness and revealed normal signal intensity, while there was a narrowing of the cervical canal at C5-C6 levels and C6-C7 levels with indentations at anterior subarachnoid space, spinal cords and bilateral exciting nerve roots at C5 C6 Levels due to mild subarticular disc protrusions.

ESR Finding

In patients with ALS, there is evidence of increased levels of C reactive protein and Erythrocyte sedimentation rate as compared to controls [8]. In our patient, there was increased ESR – 25 mm/hr.

EMG STUDIES

These are the most important component of electrodiagnostic evaluation in ALS as it allows an earlier diagnosis by indicating lower motor neuron involvement. [12]

To support a diagnosis of ALS [12]	In Our patient, there were
decreased motor unit recruitment with rapid firing of a reduced number of motor units	Reduced motor unit recruitment, maximum effort and reduced Inference pattern. In motor neurons
and/or large amplitude, long duration MUP with or without evidence of remodelling (increased number of phases)	Polyphasic volitional Motor unit Action Potentials
in combination with abnormal spontaneous activity including positive sharp waves (PSWs), fibrillations, and/or fasciculation potentials (FP)	Spontaneous activities – Fasciculation in Right biceps brachi, right dorsal interosseous, and left triceps muscles

 

Nerve Conduction Velocity studies in ALS

Findings seen in a patient with ALS (12)	Findings in our Patient
Motor Conduction studies usually reveal - asymmetric side-to-side CMAP differences, - normal CMAPs, or CMAPs with decreased amplitude, - prolonged distal motor latency, - slowed conduction velocity consistent with axon loss	Motor Conduction studies revealed - normal conduction velocity - low amplitude CMAP - normal F wave latency
Sensory Conduction studies are usually normal in patients with ALS	Sensory conduction studies were normal bilaterally in Median, ulnar and sural nerves.

 

Diagnostic and treatment modalities

According to the El Escorial revised criteria [14], the patient was diagnosed with ALS .The patient was started on Tablet Rilozule 50 mg twice a day [13]with vitamin E supplementation.

Learning outcomes

The following consultation occurred as a telecommunication, a PaJR group was created where in a discussion regarding the problems faced by the patient were understood with an aim to find answers to the patient’s questions. In this case the patient wanted a second opinion in terms of the treatment modalities for the diagnosis. After Discussion about the disease and how the treatment is limited to physical rehabilitation as drugs do not offer a through cure, the patient was less motivated to follow up which acted as a barrier in communication. SWOT analysis of this approach is as follows-

Strength:

The patient had a means of communication which was present at all times, with multiple doctors ready to provide opinions – For instance, rehabilitation facilities were explained to the patient in the PaJR group. This approach allows the best possible outcome of the patient without having to visit multiple doctors. There was a systemic medical record formed which would be helpful to the patient in the future, including the patient’s medical history, investigations, examinations at one place making it easily accessible for medical professional treating this patient in the future.

Weakness:

Lack of face-to-face consultation further lacking human touch is a major drawback as it would not form an ideal doctor patient relationship. The news to the patient would be communicated over the phone, making it difficult to understand the patient’s reaction. There was a loss to follow up in this patient reasons of which include

- Patient factors – lack of motivation (due to the fatal prognosis of the condition), lack of understanding of the motive of the platform, hesitancy to explain problems faced to multiple doctor at once.

- Physician Factors – Inability to keep a tally due to excessive number of patients

Opportunities:

this approach allowed an open discussion of the rehabilitative treatment for the patient.

Threat: 

lack of conversation

References

 

1.	Brotman RG, Moreno-Escobar MC, Joseph J, Pawar G. Amyotrophic Lateral Sclerosis. StatPearls Publishing; 2022.
2.	van den Bos MAJ, Geevasinga N, Higashihara M, Menon P, Vucic S. Pathophysiology and diagnosis of ALS: Insights from advances in neurophysiological techniques. Int J Mol Sci [Internet]. 2019 [cited 2023 Apr 24];20(11):2818. Available from: https://www.mdpi.com/1422-0067/20/11/2818
3.	Longinetti E, Fang F. Epidemiology of amyotrophic lateral sclerosis: an update of recent literature: An update of recent literature. Curr Opin Neurol [Internet]. 2019 [cited 2023 Apr 24];32(5):771–6. Available from: http://dx.doi.org/10.1097/wco.0000000000000730
4.	als - Rare Diseases India [Internet]. Rarediseasesindia.org. [cited 2023 Apr 24]. Available from: http://www.rarediseasesindia.org/als
5.	How is ALS Diagnosed and Treated? [Internet]. Hospital for Special Surgery. [cited 2023 Apr 24]. Available from: https://www.hss.edu/condition-list_amyotrophic-lateral-sclerosis.asp
6.	Brown RH Jr. Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases. In: Harrison’s Principles of Internal Medicine. Mc Graw Hill Education; p. 3141–8.
7.	Masrori P, Van Damme P. Amyotrophic lateral sclerosis: a clinical review. Eur J Neurol [Internet]. 2020 [cited 2023 Apr 24];27(10):1918–29. Available from: http://dx.doi.org/10.1111/ene.14393
8.	McCombe PA, Lee JD, Woodruff TM, Henderson RD. The peripheral immune system and amyotrophic lateral sclerosis. Front Neurol [Internet]. 2020 [cited 2023 Apr 24];11:279. Available from: https://www.frontiersin.org/articles/10.3389/fneur.2020.00279/full
9.	Ghasemi M. Amyotrophic lateral sclerosis mimic syndromes. Iran J Neurol. 2016;15(2):85–91.
10.	Matsuzono K, Suzuki M, Miura K, Ozawa T, Mashiko T, Koide R, et al. Higher incidence of cervical spinal cord compression in amyotrophic lateral sclerosis: a single-institute cohort study. Neurol Sci [Internet]. 2022 [cited 2023 Apr 24];43(2):1079–86. Available from: https://pubmed.ncbi.nlm.nih.gov/34287724/
11.	Rocha AJ da, Maia Júnior ACM. Is magnetic resonance imaging a plausible biomarker for upper motor neuron degeneration in amyotrophic lateral sclerosis/primary lateral sclerosis or merely a useful paraclinical tool to exclude mimic syndromes? A critical review of imaging applicability in clinical routine. Arq Neuropsiquiatr [Internet]. 2012 [cited 2023 Apr 24];70(7):532–9. Available from: https://www.scielo.br/j/anp/a/VT7b4zZPdVk6gfmrTrQ4pnQ/?lang=en
12.	Joyce NC, Carter GT. Electrodiagnosis in persons with amyotrophic lateral sclerosis. PM R [Internet]. 2013 [cited 2023 Apr 24];5(5 Suppl):S89-95. Available from: http://dx.doi.org/10.1016/j.pmrj.2013.03.020
13.	Chen JJ. Overview of current and emerging therapies for amyotrophic lateral sclerosis [Internet]. AJMC. 2020 [cited 2023 Apr 24]. Available from: https://www.ajmc.com/view/overview-of-current-and-emerging-therapies-for-amyotrophic-lateral-sclerosis
14.	Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord [Internet]. 2000;1(5):293–9. Available from: http://dx.doi.org/10.1080/146608200300079536 15. Link to the first article https://dr-arefin.blogspot.com/2022/11/59f-with-als.html

Case Discussion on Pajr Group : 

[11/21/22, 9:44:34 PM] Arefin Sadat: Greetings!

[11/21/22, 9:45:34 PM] Arefin Sadat: https://dr-arefin.blogspot.com/2022/11/59f-with-als.html


Here is the updated case report with deep tendon reflex videos of the patient: 59F with ALS
[11/21/22, 10:20:12 PM] Patient 59F: New symptom we found today , according to her it's very old , below video FYR

[11/21/22, 10:41:48 PM] Dr. Rakesh Biswas sir: Looks like brachial artery pulsations

.
[11/22/22, 4:16:03 PM] Patient 59F: is there any medical center to take her for treatment, please suggest

[11/22/22, 4:20:16 PM] Dr. Rakesh Biswas sir: All medical centers will examine her and may offer some treatment but once they too clinically confirm the diagnosis of ALS there isn't much effective treatment medical science has been able to discover till now for this condition.


Most centers can try to find solutions to support her current activities using what are currently called neurorehab tech.


Please share her hourly activities here so that we can assess her current requirements

[11/22/22, 4:25:08 PM] Patient 59F: Sir , she dosen't have strength on her waist to Stand or walk, please advise if there is any treatment / surgery which can help her

[11/22/22, 4:34:03 PM] Dr. Rakesh Biswas sir: As per the data you have shared till now through this could be ALS in which case surgery is not available but for any paraplegic one of the neurorehab solutions available in US is "exoskeleton" and other devices.


You can read more about them here https://link.springer.com/article/10.1007/s00415-022-10971-w

Some of our team members are researching on these technologies. @ Dr Arefin  may be able to put you in touch with our team member and robotics expert, Abhishek Choudhury who is also there in our PaJR volunteers group

[11/23/22, 8:33:02 AM] Dr. Avinash Kumar Gupta: For this case


- do they use well water for drinking or other household purpose?


- What filter they use for drinking water?


- please share her district and state name.


Well water is associated with sporadic ALS caused by probably fungal infection or inorganic toxins like selenium. Lead toxicity also one possibility due to sindur, so can we know if she is hindu?


What is his husband's age and how is his health?

[11/23/22, 8:33:37 AM] Dr Rakesh Biswas sir: Share all the references too

[11/23/22, 8:47:28 AM] Dr. Rakesh Biswas sir: Share clickable links too

[11/23/22, 8:49:03 AM] dr Avinash Kumar Gupta: https://pubmed.ncbi.nlm.nih.gov/16909025/

The importance of questions is, if she consumes water from well, can stop that. If it's in a district where water toxicity with metals are common then we may look into research to find ALS scenario there as sometimes toxicity treatment may help symptoms. If filter at home then better if family members consume water from that and avoid from well if we find possible connection.

[11/24/22, 12:12:25 PM] dr. Avinash Kumar Gupta: So whenever possible, you may find answers from patient or their family.

[11/24/22, 2:34:26 PM] Patient : we have RO machine , from there we are Drinking water

[11/24/22, 7:04:07 PM] Dr. Rakesh Biswas sir: Does she use a wheel chair?

[11/24/22, 7:17:47 PM] Patient 59F: No sir

[11/24/22, 7:40:44 PM] Dr. Rakesh Biswas sir: Is she able to walk nowadays?

[11/24/22, 7:45:23 PM] Patient : No she is not able to walk, she need support to walk, once we hold her hand with that she is walking with very slow step

[11/24/22, 7:48:57 PM] Dr. Rakesh Biswas sir: Alright that means she can walk with support.


How long does she walk daily?


Is she able to walk from her bed to the bathroom and able to look after herself?
[11/25/22, 10:52:07 PM] dr. Avinash Kumar Gupta: Any ayurvedic medication use by the patient now, recently/ recent past?


Please list all if used with duration used for.


They sometimes cause lead toxicity.

Discussion on Pajr Volunteer's group :

[20/11/2022, 3:12 pm] Dr. Rakesh Biswas sir : Thanks.

From the notes can you make out what are her reflexes like?

Can you make the son learn how to elecit deep tendon reflexes and share the video?

You may have noticed how your previous 39F with neurodegenerative myelopathy was so very slowly progressive while this one progressed very quickly

[20/11/2022, 3:16 pm] Dr. Arefin Sadat: Okay, sir, I am looking into it & will update this with the reflex note and video.
[20/11/2022, 3:32 pm] Dr. Charan Sir : Thank you. So according to you it is - Rapidly progressive sensory motor demyelinating polyneuropathy with spinal cord indentation at C5-C6 and C6-C7.

Peripheral polyneuropathy is like LMN and Compressive myelopathy is like UMN. Reflexs would helpful here.

[20/11/2022, 3:39 pm] For this case one thing I would like to add. While talking with pt I learnt that she can't lift her legs from bed when lying down i.e lost antigravity movement. She can only slide her legs on bed.


[20/11/2022, 3:41 pm]Dr. Charan Sir : Then possible power in her both legs would be 2/5.


[20/11/2022, 4:30 pm] Dr. Rakesh Biswas sir: Yes this is a classic description of grade 2/5 power provided directly on phone by the patient.