Finally published with a changed title full text open access here :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301093/
Second draft of the paper being written collectively with local and global learning team under invitation from the American Journal of Neurodegenerative diseases :
Left:
Proper paraphrasing of content from the reference links used and adding missing content from some of the cases described here.
ABSTRACT (IMRAD format):
Introduction:
Single case studies are research studies of single participants. They explore new ideas and can suggest extensions in methods and for treatment (Yin, 1984).
Methodology:
We utilized a single case study seed design in a series of patients with neurodegenerative disorder attending the medicine and Psychiatry services of our rural medical college catering to a district population of 2,000,000
Results: A thematic analysis of each single case data was done and themes tabulated.
Discussion:
In our patients of neurodegenerative brain disorder we find common ground in their presentation as a movement disorder along with psychiatric symptoms and later going on to develop different course of events during their illness. We postulate that movement disorder is an obvious logical bio-clinical marker toward organic psychopathology of psychiatric symptoms found in neurodegenerative disorders and detailed study of the accessible events in these patients can offer newer insights to the organic nature of psychiatry.
References:
1.Joyce, E., 2018. Organic psychosis: The pathobiology and treatment of delusions. CNS Neuroscience & Therapeutics, 24(7), pp.598-603.
https://www.ncbi.nlm.nih.gov/
2) Price, A . Single case studies as seeds. Int J User-Driven Healthcare 2014; 4: 43–50.
3) Yin, R. K. (1984).Case study research: Design and methods. Newbury Park, CA: Sage
4) https://movementdisorders.
INTRODUCTION:
In recent times, the distinction between organic and functional psychoses has become blurred and these are better described as primary and secondary psychoses, where “secondary” refers to there being an identifiable pathogenic substrate.1
The pathophysiology of psychosis and the role of motor circuits in the development of psychosis in neurodegenerative disorders is complex but few hypothesis suggest that lesions of the right lateral prefrontal cortex or its efferent projections, such as the basal ganglia and limbic system, are associated with delusions while frontostriatal circuitry disruption after loss of neurons, as in caudate atrophy may alter relevant processing of striatal‐limbic information and favor the development of psychosis.
In addition to structural alterations, faulty dopamine signaling, including altered dopamine receptor modulation, has been proposed as a possible pathway for the genesis of delusions and in summary brain mechanisms underlying delusional symptoms may be similar in both primary and secondary psychosis which needs further research.
(https://movementdisorders.
To further explore the above hypothesis that a better understanding of organic psychopathology of psychiatric symptoms particularly in neurodegenerative disorders can be gained from a detailed study of the accessible events, we utilized a single case study seed design in a series of patients with neurodegenerative disorder attending the medicine and Psychiatry services of our rural medical college catering to a district population of 2,000,000 and below is a detailed qualitative description of what we found followed by a tabulation of the emerging themes.
CASE SERIES:
CASE 1:
A 50 year old man, a married farmer presented to our hospital with the complaints of frequent falls, involuntary movements of his distal upper limbs and self talking since 1 year.
On further interviewing his wife, she gave a history of him falling from his bike 2 years back after the patient had a sudden blurring of vision. He however sustained no head injury during the accident but attained fracture of his left tibial bone for which open reduction & internal fixation was performed. She revealed that he was a regular alcoholic with a daily consumption of 90 ml of whiskey and chews around 5 tobaccos everyday. Since the past 1.5 years his wife tells us that he has been having frequent falls, he would frequently walk into objects. She described him to ‘walk straight’ without turning his head.
She described her husband to be an aggressive individual and would often get into quarrels in matters which weren’t of his concern. However, since the past 1 year he had been socially distancing himself, has reduced expressing himself emotionally. He would often complain of hearing strange voices.
Since the past 7 months, he had to visit local hospitals a couple of times for weakness in his lower limbs and had to receive potassium correction because of recurrent hypokalemia. He has been on Potassium Chloride oral supplementation ever since.
2 months back, he was evaluated for his symptoms and a CT brain along with an EEG was done which showed a normal study. He was diagnosed with Parkinson’s disease and was started on Syndopa 110mg and Trihexyphenydryl 2mg twice a day.
On presentation to us, he was conscious, coherent and oriented to time, place and person. His MMSE was 30/30. He had mask like facies, he had no expressions on his face while interacting. He had a stooped posture and on observing his gait, he had a festinating gait and would walk straight without turning his head. He also had reduced arm swing.
His muscle tone was increased in all the four limbs and his biceps, triceps and knee reflexes were exaggerated, his plantar reflex showed flexion. On cranial nerve examination, he was not able to perform upward or down ocular movements.
On further evaluating the case, his metabolic parameters were within the normal range.
MRI BRAIN showing mild cerebral atrophic changes
He was put on Tab Syndopa 110mg thrice a day, Tab Quetiapine 25 mg once a day.
CASE 2:
Mr. X, a 66 years, right handed, uneducated, married farmer, hailing from rural background of Sate of Telangana with pre-morbidly well adjusted without any significant past or family history of mental illness presented to our psychiatric inpatient services on 9th July, 2018 with his wife for gross rigidity in body, asymmetric tremors since 4 to 5 years and visual hallucinations, memory deterioration, disinhibited behavior, fearfulness, early & middle insomnias and episodes of aimless wandering since last 2 years. His voice became muffled and lower in intensity and would answer only in one or two words than to his previous self. His family members noted that pace of his gait and normal arm swings were remarkedly reduced by the end of December 2015. He was shown to neurophysician in nearby district hospital 3 years before and was started on twice a day combination of Levodopa/Carbidopa (110mg). However, there was only little response and his shaky, pill-rolling movements of distal hands were gradually increased in frequency, intensity and duration with a typical static pattern getting incapacitated to hold any objects over a period of last 6 months. For his disinhibited behavior he was given 5 mg of haloperidol for a week by private psychiatrist after which his rigidity and bradykinesia worsened and he further developed confusion when he was put on 6 mg/day of trihexyphenidine as he stopped identifying people visiting his home and episodes of disinhibited behavior, talking to self, visual hallucinations, fearfulness, delusion of persecution, aimless wandering increased. He began reporting that he could see some strange people standing in front and observing him, running in his verandah, at other times he would behave as if his relatives were sitting beside his bed and he screamed few times as if snakes were crawling around his bed/house. His self-care, social interactions with his friends and his usual activities like going to vegetable market and attending social functions were almost stopped. There was no history of headache, seizures head injury or vomiting in morning (r/o intra cranial SOL), neither there was history hyperorality and hypersexuality, repeated, over ritualistic activities (r/o specific syndromes) or thought alienation or other SFRS (r/o schizophrenia).
On examinations, he did not have any fever, signs of meningeal irritations, spine or cranium deformity. He was conscious, oriented to time and place but was confused about persons around him. His mood was depressed and labile. Perceptual distortions were present. His cognitions were impaired (MMSE done on 09/12/2018 -11/30), his memory registration and retrieval were poor and there were gross deficits in recent, remote and working memory. His speech was muffled, low volume, curtailed and monotonous without any inflections or prosody. His judgement, praxis, simple calculations, object naming, logical thinking and insight was impaired. His posture was stooped and gait was festinating. He had symmetrical tremulousness of his distal upper limbs with typical 6 Hz frequency, coarse, pill rolling tremors, predominant contraction and relaxation of flexor and extensor with less prominent rotatory component between finger and thumb. His tone in muscles and joints were increased as he showed cog-wheel type of rigidity on clinical evaluation. His cranial nerves were normal. His vitals and other systemic examinations were essentially normal. He was hospitalized and comprehensive assessments were done. His neuroimaging showed gross generalized frontal atrophy.
An Axial T2 Weighted Magnetic Resonance Imaging in index patient showing asymmetric cerebral atrophy extending to the central sulcus with mild, generalized enlargement of fronto-temporo-parietal sulci and mild decrease signal intensity of basal ganglia with apparently normal width of pars compacta in substantia nigra without any clear depigmentation or any blurring or thinning in contrast to what is typically seen in Parkinson’s Disease (Figure 1 A).
There is also an evidence of mild thinning of post-central gyrus on left > right side but not of pre-cental gyrus or central gyrus indicating initial stage of cortico-basal degeneration (Figure 1 B).
Midbrain tegmentum area appear smaller in size than normal, however, pons and cerebellar volumes are apparently normal and there are no T2 hypointensities in either of putamen or caudate nucleus ruling out Multiple System Atrophy (Figure 1 C).
At our hospital, he was diagnosed as Parkinson’s Plus Syndrome (Idiopathic Parkinson’s disease with Dementia and Cortico-basal degeneration ) and admitted in inpatient psychiatric services. He was started on Quetiapine 50 mg HS, his Syndopa (110 mg/day) dose was increased to thrice a day, 10 mg morning memantine was started for his dementia which gradually increased to 20 mg/day. 60 mg Propranolol was added for his tremors. 2 mg of Lorazepam was given in initial first few days for his sleep disturbances along with quetiapine. His serial MMSE was done weekly which started improving a 3 to 4 points score over 12 to 16 weeks of time (MMSE Score on 9 th April 2019 was15). His ADS Cog Score improved from baseline 26 to 36). His hallucinations, delusions, disinhibitory & wandering behavior showed markedly improved so as his sleep and personal care. He was trained for helping finish his routine and basic needs and use of directions specific symbols and behavioral principles were taught to family. His bradykinesia, tremors mildly reduced but his rigidity continued, and in last 6 months or so, he again started deteriorating markedly in cognitive functions (MMSE score in October 2019 was 10), developed apathy and worsened in his parkinsonian symptoms specially rigidity and akinesia and was not responsive to even QID Levodopa (110 mg). Eventually in January 2020, he developed difficulty in identifying relatives, upper limb myoclonic jerks and dystonia in neck and upper limbs leading to dysphagia. We increased the dose of Mimentine to 30 mg/day and added Tab Rivastigmine 3 mg/day, Tab Clonazepam 6 mg / day and stopped lorazepam while continued others, however, there was no specific improvements and patient became bed ridden and his quality of life deteriorated rapidly.
Case 3:
A 67 year old married woman presented to our hospital along with her husband and daughter complaining of Involuntary movements of right forearm since 4 months, Involuntarily movements of left index finger and thumb since 4 months.
Since 4 months , her husband started noticing involuntary movements of her right forearm which would be more at rest and would also be present during her sleep. Over the next few days, she developed involuntary movements of her left Index finger and thumb following which she even developed on and off involuntary movements of her tongue.
Since the last 20 days, he says she hasn't been involving herself in conversations and stopped responding to people or would sometimes respond late.
On examination, she was conscious, oriented to time, place and person though not willing to communicate or respond to the asked questions. She had mask like facies. She also had asymmetrical rhythmic small amplitude movements of distal muscles of her right forearm and pill rolling tremors observed involving left thumb and index finger, occuring even at sleep. Her tremors were present at rest and absent on motor activity. She had slow initiation of motor activity and delayed verbal response. Her limbs had lead pipe rigidity present and all her reflexes were exaggerated. On cardiovascular system examination, she had a systolic murmur heard in aortic area till apex.
Her laboratory investigations were within the normal range. Her 2dEcho revealed severe aortic stenosis, concentric LVH with an ejection fraction of 55%.
Her MRI Brain showed mild cerebral atrophy, tiny calcifications with no edema in right lentiform nucleus and left temporal lobe, small vessel ischaemic changes.
She was diagnosed with Parkinson’s disease and was discharged on Tab Syndopa 110mg thrice a day.
She was discharged on Tab Syndropa 110mg thrice a day along with Tab Neurobion Forte.
She reviewed to our hospital after one month happy with the results and told us that her tremors have comparatively reduced.
She reviewed back after 2 months of using Tab Syndropa 110mg thrice a day, complaining of increased tremors in her distal upper limbs. Her dose was escalated to Tab. Syndopa Plus 125 mg QID.
CASE 4:
A 49 year old English and Telugu language lecturer presented with a 2 month history of progressive asymmetric involuntary movements of his right index and middle fingers.
The patient reports that he first noticed them happening nearly 6 months ago, which was very small in amplitude, affecting these two fingers only. He attests that these movements often worsened with rest and abated with activity. They were not troublesome initially but since the past 2 months he has been unable to correct answer sheets because of the involvement of his thumb and maintaining stability of his hand was proving difficult. He describes these movements as involuntary, rhythmic to and fro oscillations.
He also adds that his handwriting has become ugly with very small letters. On interviewing further, the patient reports that he feels stiffness in his wrists (Right>Left), which has now ascended to his elbows. He says the stiffness is present throughout the range of motion. He also says that since the last 1 month, the same involuntary movements also started appearing in his left hand.
At this point, he also says that his walking has become difficult with small, short steps and a forward stoop, and he feels that although he weighs 60 kgs, he feels like it weighs 100 kgs.
He does not report any difficulty in reading the newspaper, holding the paper, turning pages or folding it back. He does not have any difficulty in brushing his teeth or combing his hair. He also denies having difficulty in holding objects, such as holding a water bottle to drink nor any difficulty in mixing food and eating it. He does not have any difficulty in wearing a vest or in buttoning or unbuttoning of his shirt. No difficulty in lifting his lower limbs and wearing a trouser.
The interview continues and we question for any difficulty in taking the stairs - he reports that he has been having difficulty in taking stairs up, in that he feels he sometimes might lose balance. He has no difficulty in descending stairs. The patient also denies having swaying of his trunk while walking or overshooting his hand while picking up objects.
On pressing further - he reports that he hasn't been having morning erections since 2 months and also reports a loss of sexual desire. He also says that since 2 months his bowel habits have been incredibly erratic, in that he sometimes has an immediate urge to defecate when he has tea and sometimes goes 2 to 3 days with constipation.
He, however, denies feeling dizzy or lightheaded when waking up in the morning. He denies having stiffness in his lower limbs, denies cotton wool sensation of floor, denies burning pain or inability to feel hot or cold stimuli. He also denies buckling of knees but, however, he reports that he has been having a great difficulty to walk in the dark since 2 months and says that he feels like he would definitely fall without support.
His brother gives a positive affirmation for all his symptoms and also says that he previously used to be a fairly jovial and hardworking man with good oratory skills, however, since the last 2 months he says his brother's speech lacks that 'edge' which he previously had. On asking further, the brother says that he has been speaking in a monotonous drab since 2 months.
The patient denies ever having urinary incontinence, memory deficits, the brother vehemently denies the patient ever being anti-social, he does not have any difficulty in forming new memories or any visual deficits.
He has no relevant past or family medical history.
On presentation, the vitals of the patient were stable. His MMSE score was 29/30. Cogwheel rigidity was noted at his right wrist, Tongue tremors & microphagia were present. On foot tapping examination, movements of his right lower limb were found to be slower than his left lower limb. He had a postural blood pressure drop, on supine posture his bp was 180/110mmhg and on checking his blood pressure after 3 minutes in standing posture it was 160/90mmhg.
The patient was started on Tab Syndopa 110mg 4 times a day.
CASE 5:
A 58 year old man, married, saree maker by occupation presented to our hospital with the complaints of
Slurring of speech since 6 months, deviation of mouth to the right along with smacking of lips since 6 months, urinary incontinence since 6 months and forgetfulness since 3 months. Patient puts designs on sarees but since the past 1 year he couldn't put it properly so according to his wife, his threading wouldn't look good and at times, they would get complaints from customers regarding that, because of this he was asked to quit working.
Patient previously would get up daily, take a shower and daily visit a temple nearby but since the past 8 months the patient would get God's idols from the temple and they were found in his pockets and also in his room. When asked, he denied getting them home. They stopped allowing him from going to temples.
Since the past 6 months patient would just sit at home and he slowly developed slurring of speech.
Since that past 5 months, his wife says the patient has been forgetting names of tools with which they would put design on sarees. He is able to recollect it after around 10 minutes or if prompted, though he was able to recall people's names. He stopped going for shower by himself unless prompted to. He has not been shaving his beard by himself as he used to previously do, his son started shaving his beard for him.
4 months back his second son got married. He did not take any active part in the wedding preparations, he was just sitting in one corner and wasn't able to recognize people at the wedding and he only interacted with the ones who were introduced to him by his son.
His wife says that he kept calling out his younger son by his elder son's name and was unable to recognize family members sometimes. He sometimes fears saying that he can see a snake. He hasn't been buttoning and unbuttoned his shirt.
Since the past 3 months, he is unable to fold a saree without repeated instructions. He sometimes repeats the same answer for every question asked. He has been becoming angry for small things and he calms down within 5 to 10 minutes on his own. He stopped laughing on jokes.
Since the past 2 months he has been using more of gestures to communicate and his speech has become more slurred. He was throwing away his food as he was finding it difficult to swallow it, he was even finding it difficult to swallow liquids. There was a delay in his response to commands. He left home without informing twice after which he was found by his relatives and was brought home. He has been finding it hard to urinate while he is in his pants so he has been avoiding wearing pants, wears a lungi instead.
Since the past 1 month , the slurring of his speech increased and there was deviation of mouth to the right because of which whatever he consumed drooled from the left angle of his mouth. He was even found by their neighbors roaming shirtless in a lungi since then everyone has kept an eye on him and are making sure he doesn't leave home.
He stopped consuming alcohol 3 years back, prior to that he would consume alcohol regularly, around 180 ml of whiskey weekly thrice.
8 years back, he left home for 4 years and he returned later by himself. On asking the patient the details of what he did back then, he says he visited a temple.
On presentation to us, the patient was conscious, coherent and cooperative, his MMSE score was 9/30. His speech was slurred, his fluency was impaired though his comprehension and repetition were intact. He had a Waddling gait. On performing lobe function tests, on evaluating his parietal lobe, his right to left orientation and visuo spatial orientation and construction all apraxia was lost and while evaluation the occipital lobe, prosopagnosia was lost. On cranial nerves examination, there was loss of wrinkles over the left forehead and deviation of his mouth to the right. His biceps, Triceps and supinator and knee reflexes were exaggerated. His metabolic profile was within the normal range.
His MRI Brain showing supratentorial hydrocephalus, cerebral and cerebellar atrophy along with chronic ischaemic changes.
He was diagnosed with Alzheimer’s disease and was started on Tab Donepezil 10mg once a day.
RESULTS:
Tabulation of emerging themes:
Case 1 | Case 2 | Case 3 | Case 4 | Case 5 |
Farmer | Farmer | Language lecturer | Saree maker | |
Involuntary movements of distal upper limbs | Shaky, pill-rolling movements of distal hands | Involuntary movements of right forearm, left index finger, thumb, and tongue | Asymmetric involuntary movements of right index and middle fingers, slower lower limb movement (right>left) | |
First symptom: 1.5 years ago | 4-5 years ago | 4 months ago | 2 months | 1 year ago (?8 years) |
H/O frequent fall, alcohol consumption | Postural BP drop | Alcohol consumption | ||
Straight-walk with ↓ arm swing, self-talking, aggressive behaviour, ↓emotional expression, social distancing | ↓ arm swing, self-talking, Muffled voice, memory deterioration, perceptual distortions, disinhibited behavior, fearfulness, delusion of persecution, insomnia and episodic aimless wandering, social distancing, Labile and depressed mood | Social distancing | Wrist and elbow rigidity, difficulty walking (especially in dark) and taking stairs, lack of sexual desire and morning erections, erratic bowel habit, speaking in a monotonous drab | Right sided mouth deviation,Slurriness of speech with smacking of lips, urinary incontinence, forgetfulness, answer repetitions, increased anger |
Impaired judgement, praxis, simple calculations, object naming, logical thinking and insight | slow initiation of motor activity and delayed verbal response | Dysphagia, delayed response to commands, | ||
Auditory hallucination | Visual hallucination | |||
Mask like facies, stooped posture | stooped posture | Mask like facies | ||
Festinating gait | Festinating gait | Waddling gait | ||
Recurrent hypokalemia | Severe aortic stenosis, concentric LVH | |||
Hypertonia in all limbs, exaggerated biceps, triceps, knee reflexes, flexor plantar reflex | Cog-wheel type of rigidity, gross rigidity in body, symmetric pill rolling tremors in distal upper limbs, bradykinesia | Lead pipe rigidity, exaggerated reflexes, asymmetric pill rolling tremors, resting tremors, | Cogwheel rigidity, tongue tremors & micrographia | Exaggerated biceps, Triceps and supinator and knee reflexes |
Failed upward or downward ocular movements | Normal cranial nerves | Loss of wrinkles over the left forehead, deviation of mouth to the right | ||
Normal MMSE | Low MMSE | Normal MMSE | Low MMSE | |
Normal EEG and brain CT | ||||
MRI brain: mild cerebral atrophy | MRI brain: | MRI brain: | MRI brain: supratentorial hydrocephalus, cerebral and cerebellar atrophy along with chronic ischaemic changes | |
Parkinson disease | Parkinson’s Plus Syndrome (Idiopathic Parkinson’s disease with Dementia and Cortico-basal degeneration) | Parkinson disease | Alzheimer’s disease | |
Levodopa and Carbidopa, Trihexyphenidyl, Quetiapine | Levodopa and Carbidopa, haloperidol, trihexyphenidyl, quetiapine, memantine, propranolol, lorazepam, | Levodopa and Carbidopa, vitamin B1, B6, B12 | Levodopa and Carbidopa | Donepezil |
No comments:
Post a Comment