Neuronal degenerations 🧠🕵‍♀️

Being a resident in a tertiary center is like a blessing in disguise with lots of learning opportunities and a wide range of patients to work with from admission until discharge. This is a compilation of a few such cases that aroused my interest in the field of neuroscience.

 I've penned down a few experiences during my residency in the Department of General Medicine.

One case involved a 45-year-old male in the outpatient department. He had jerking movements in his arms and legs, and his sister, who was sitting beside him, had similar movements with less intensity. 

This made me wonder about the microscopic structures called neurons that control these visible movements, which are under the control of genetic material within cells. 

Further investigation revealed a family history of similar complaints, suggesting an autosomal dominant mode of inheritance. 

After conducting a thorough clinical examination, history, and pedigree chart, we discovered that there was a family history of similar complaints, suggesting an autosomal dominant mode of inheritance. We narrowed down our differentials to SCA and Huntington's disease.

We followed up with a visit to a geneticist to get their genes tested, and they were diagnosed with Huntington's disease. This experience made me realize the value of the role of genes in evolving medical sciences and neurodegeneration, as well as the variability in the severity of the disease based on the number of CAG repeats in the individual(siblings).

 It also made me question how the neuronal toxicity selectively destroys the striatum, which was partly answered here

evidence from vertebrate and invertebrate models of HD indicates that expression of the polyQ-expanded form of huntingtin results in early impairment of axonal transport and mitochondrial function. As well, alteration in activity of the N-methyl-d-aspartate (NMDA) type glutamate receptor, which has been implicated as a main mediator of excitotoxic neuronal death, especially in the striatum, is an early effect of mutant huntingtin. Proteolysis and nuclear localization of huntingtin also occur relatively early, while formation of ubiquitinated aggregates of huntingtin and transcriptional dysregulation occur as late effects of the gene mutation. Although each of these processes may contribute to neuronal loss in HD, here we review the data to support a strong role for NMDA receptor (NMDAR)-mediated excitotoxicity and mitochondrial dysfunction in conferring selective neuronal vulnerability in HD.

 

https://pubmed.ncbi.nlm.nih.gov/16984809/

This case opened up a potential area of research - AI in managing Huntington's chorea. AI has the potential to revolutionize the management of HD by providing personalized, predictive, and preventive care. AI can help in the early diagnosis of HD by analyzing large datasets of clinical, genetic, and imaging data.

 It can also help in the development of new therapies by identifying new drug targets and rehabilitation.

Detailed history clinical examination and Followup discussion in the PaJr has been referenced here - 

https://96sanjanapalakodeti.blogspot.com/2022/09/47m-with-uncontrolled-hand-movements.html

https://96sanjanapalakodeti.blogspot.com/search?updated-max=2023-05-22T10:01:00-07:00&max-results=7

A 61 year mason was brought with complaints of shortness of breath ,fever and cough from 10 days as quite common presentation

to the medicine opd was thought of Pneumonia or flu

but what caught our eye was his involuntary movements of upperlimbs which made us delve deep into his history of involuntary

movements from past 3 years for which he has been in search of cure ,but all of his attempts have been futile.

The movements resembled characteristic pin rolling movements and examination of hypertonic limbs lead us to make a provisional diagnosis of 

Pneumonia with parkinsonism with mild hepatospleenomegaly

When the labs returned we were blown away  by bicytopenia and markedly elevated leucocytosis ,which was assumed either due to ?Leukamoid reaction or malignancy(?CMML)

With persistantly high counts of wbc with left shift made us go for bone marrow biopsy with the results are awaited

next day patient had sudden onset altered sensorium was evaluated and found to have euvolemic hyponatremia

this lead us futhur to ? SIADH ?Carcinomatous meningitis

with the correction of Sodium, improvement is seen in sensorium

hypercalcemia, elevated gamma gap ,positive Bence jones protein test with bonemarrow biopsy showing plasma cell dyscrasia

provisional diagnosis of multiple myeloma has been made and patient had been followed up through the

Pajr group and information continuity was made possible through this means

this made me question the association of neurodegenerative disorders in malignancy or was it just an incidental one?

review of article showed the association and pathophysiology of neurodegenerative disorders in malignancy 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519136/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009676/

detailed description of the case with the pajr description been linked here

https://munukutlasaimythili.blogspot.com/2022/09/a-case-of-50-year-old-man.html

Going through this reminded me of another case much similar to its association

37 year old male was brought to our department by the members of the society he is working in with 

bowel and bladder incontinence

erectile dysfunction and weakness of limbs , interesting to note that he started associating these to the snake bite he had 10 years

back and was asymptomatic for period of 5 years in between ,his visits to multiple hospitals were futile

obtaining history from him made us think of familal /herediatry disorder with speech disturbances and weakness

Examining him made us realise the central cause and suggested MRI

MRI report took us by surprise with lesion in spinal cord suggestive of ependymoma or astrocytoma

follow up with neurosurgery and

 is there really any association of malingnancy in neurodegenerative disorders

if not now is he more susceptible to it?

detailed description of patient and pajr discussion here-

https://himajav.blogspot.com/2023/03/37m-snake-bite.html

working on a thesis with stroke made me realise its close association with neurodegeneration

here are the list of few cases seen with stroke and encephalomalacia

this helped me broaden the idea behind neurodegeneration which is quite often used for alzheimers,huntington or parkinsons

degeneration though most commonly seen in elderly can also occur in the younger or early onset degenation can be seen

links of blogs here-

https://jharipriya.blogspot.com/2022/09/cva-pca-stroke-with-acute-infarct-in.html

https://ankurkumar14.blogspot.com/2022/07/50-year-old-man-with-weakness-in-lower.html

http://tejasridevaruppala36.blogspot.com/2023/05/acute-cerebrovascular-accidentleft.html

https://rishitharaok.blogspot.com/2023/05/35-female-with-diminision-of-vision-in.html

Encephalomalacia also known as cerebromalacia, is the softening of brain tissue. It can be caused either by vascular insufficiency, and thus insufficient blood flow to the brain, or by degeneration. Encephalomalacia can be the formation of necrosis, or dead tissue, in a portion of the brain due to a partial complete blockage of blood flow to the area, which in turn can be caused by a natural condition or by infection or trauma (TBI). The term encephalomalacia is also used at times to refer more generally to degenerative conditions affecting the brain. If the condition affects the white matter of the brain, it is called leukoencephalomalacia. If it affects the gray matter, it is known as polioencephalomalacia.

https://www.passenpowell.com/encephalomalacia-brain-injury-children-adults/

https://onlinelibrary.wiley.com/doi/10.1111/jnc.14157