Below some links with some texts
Some background: The below gives somewhat new perspective to my multifaceted hypothesis diagnostic work based on my own complex symptoms history from first year of life started with that I tied the sheets to the bed so that I wouldn’t hurt myself when I was on my knees and pounded my head into the wall.
Tied up, I could move one leg back and forth the whole time, which obviously had a calming effect on me during sleep. I had this rhythmic movement for about 50 years before it slowed down – partly probably because from 1975 (when the Beta endorphin system was discovered – I gave, among other things, a Nobel Prize, which I heard on a science program on the radio when it became known. At the same time, this was associated with jogging, which led me to start jogging in 1975, which at first had extreme emotional fluctuations, but since I had received the information above, I continued anyway (was a musician and pianist at the time).
The emotional stability that then developed over the next 10 years completely changed the way I deal with biopsychosocial stress. Only after passing 80 (as a professor of psychophysiological behavior medicine) do I now begin to see connections with the initial conditions and the very intractable permanent since 3 years sound alarm. The above may be good to have in the background when I present below some links/texts that may have bearing on hypothesis diagnosis development!
Now the links
2022-10-08 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202748/
“A broad set of conditions may present with an exaggerated startle reflex in clinics. This, combined with the overall rarity of these disorders, may pose diagnostic uncertainty in the mind of the treating physician. Herein, we report a case of a patient who presented to us with the complaint of exaggerated startle reflex and outline a simple approach towards characterization of these disorders … Episodic ataxias – These are characterized by short lived brief attacks of ataxia with normal cerebellar function in between attacks. There are various types (1–7) and attacks in EA. EA-1 may be triggered by sudden movements, physical and emotional stress, and also by startle.13 Patients may have up to 30 attacks per day. In between these episodes, patients have varying degrees of neuromyotonia1. EA-1 is a potassium channelopathy caused by mutation in KCNA1 gene. The dysfunction of this channel leads to neuronal hyperexcitability. Acetazolamide, a carbonic anhydrase inhibitor, is the drug of choice.3 Overall, EA-2 is the the most common subtype with attacks provoked by exercise, physical and emotional stress. Between the attacks, these patients may be normal or may have nystagmus and mild baseline ataxia.13 The other subtypes are rare with later age of onset (EA-4 and EA-5) and sometimes variable features between the attacks, such as tinnitus, vertigo and diplopia (EA-3), migraine (EA-6). The features in EA-7 are similar to EA-2 but without the clinical findings seen between the attacks.13”
1 Isaacs’ Syndrome “Issacs’ syndrome (also known as neuromyotonia, Isaacs-Mertens syndrome, continuous muscle fiber activity syndrome, and quantal squander syndrome) is a rare neuromuscular disorder caused by hyperexcitability and continuous firing of the peripheral nerve axons that activate muscle fibers” https://www.ninds.nih.gov/health-information/disorders/isaacs-syndrome#:~:text=Issacs’%20syndrome%20(also%20known%20as,axons%20that%20activate%20muscle%20fibers.
Episodic ataxias – “People with episodic ataxia have recurrent episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraine headaches, blurred or double vision, slurred speech, and ringing in the ears (tinnitus)” https://medlineplus.gov/genetics/condition/episodic-ataxia/#:~:text=People%20with%20episodic%20ataxia%20have,in%20the%20ears%20(tinnitus).
Otoneurological Abnormalities in Patients with Friedreich’s Ataxia – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5205522/ “The most evident neurotological symptoms were incoordination of movement, gait disturbances, and dizziness. Alterations in vestibular examinations occurred in 90% of patients, mostly in the caloric test, with a predominance of deficient central vestibular system dysfunction.”
Misdiagnosis of “Very-late-onset Friedreich’s ataxia: diagnosis in a kindred with late-onset cerebellar ataxia” https://pubmed.ncbi.nlm.nih.gov/31467149/ “Friedreich’s ataxia is classically considered a disease with onset in the first or second decade. However, late-onset (age of onset 25-39 years) and very-late-onset (age of onset >40 years) forms do occur rarely. Misdiagnosis is common, particularly because the later onset forms of Friedreich’s ataxia commonly do not show characteristic features of the disorder (areflexia, dysarthria, sensory neuropathy, extensor plantars, amyotrophy, cardiac involvement, diabetes mellitus, scoliosis). Also, there may be atypical features such as spasticity, brisk reflexes and laryngeal dystonia. We present the clinical, imaging and genetic findings of a kindred with very-late-onset Friedreich’s ataxia and discuss the pitfalls and risk of misdiagnosis.”
Ataxia – https://www.mayoclinic.org/diseases-conditions/ataxia/diagnosis-treatment/drc-20355655
“An MRI can sometimes show shrinkage of the cerebellum and other brain structures in people with ataxia. It may also show other treatable findings, such as a blood clot or benign tumor”
O.R. & Startle response, Hereditary hyperekplexia & Myoclonus
2022-10-08 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202748/#:~:text=The%20’startle’%20(Greek%3A,to%20a%20sudden%20unexpected%20stimulus.&text=Evolutionarily%2C%20it%20can%20be%20considered,action%20(fight%20or%20flight
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202748/
Approach to exaggerated startle reflex: a case of hyperekplexia minor “The ‘startle’ (Greek: sudden shock or alarm) reflex (SR) is a physiological phenomenon that occurs in response to a sudden unexpected stimulus.1 Evolutionarily, it can be considered a protective reflex which orients the body towards the perceived threat and prepares it to take an appropriate action (fight or flight).2 The reflex is mediated by the caudal brainstem and consists of a generalized, symmetrical and synchronous activation of muscles causing flexion at the neck, trunk, elbow, hips and knees along with facial grimace and abduction of shoulders1; the movements predominantly involving the upper body. The inciting stimuli are mostly auditory and tactile but can also be visual and vestibular. This normal phenomenon may become exaggerated in terms of magnitude and lack of habituation, and a lower threshold, referred to as ‘exaggerated startle reflex’.1 3 An exaggerated SR has broad differential and given overall rarity, poses a diagnostic challenge. We report a case of exaggerated SR and discuss all the diagnostic possibilities with etiological categories and clinical features helpful in characterization”
“One indication of the critical role of inhibitory pathways in startle is an identified genetic disease of startle circuits called hyperekplexia*, or familial startle disease. This is characterized by exaggerated startle responses and a reduction of habituation. The disease results from a mutation in the α subunit of the glycine receptor that alters the strength of inhibition. A balance between inhibition and excitation regulates the threshold of startle responses and a shift of this balance toward excitation by the mutation may explain the enhancement of startle in the disease.” https://www.sciencedirect.com/topics/neuroscience/startle-response
* Hereditary hyperekplexia “Other signs and symptoms of hereditary hyperekplexia can include muscle twitches when falling asleep (hypnagogic myoclonus**) and movements of the arms or legs while asleep.” https://medlineplus.gov/genetics/condition/hereditary-hyperekplexia/
(?Behandling? ” Klonazepam, summaformel C15H10ClN3, är ett antiepilepsimedel, muskelavslappnande och psykoaktivt lugnande läkemedel som tillhör läkemedelsgruppen bensodiazepiner. Varunamn i Sverige är Iktorivil.” https://sv.wikipedia.org/wiki/Klonazepam)
(!! Behandling svår tinnitus ” Results Comparing before and after each drug, clonazepam significantly improved tinnitus loudness (74% of subjects), duration (63%), annoyance (79%), and tinnitus handicap inventory score (61%), whereas the G biloba showed no significant differences on any of these measures”. https://jnnp.bmj.com/content/83/8/821.short#:~:text=Results%20Comparing%20before%20and%20after,on%20any%20of%20these%20measures.
** “Myoclonus is a sudden, brief involuntary twitching or jerking of a muscle or group of muscles. It is a clinical sign and is not itself a disease. The twitching cannot be stopped or controlled by the person experiencing it. Myoclonus can begin in childhood or adulthood, symptoms ranging from mild to severe” https://www.physio-pedia.com/Myoclonus
Tinnitus .. Exaggerated startle reflex: a case of hyperekplexia minor
2022-10-08 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202748/
“A broad set of conditions may present with an exaggerated startle reflex in clinics. This, combined with the overall rarity of these disorders, may pose diagnostic uncertainty in the mind of the treating physician. Herein, we report a case of a patient who presented to us with the complaint of exaggerated startle reflex and outline a simple approach towards characterization of these disorders … Episodic ataxias – These are characterized by short lived brief attacks of ataxia with normal cerebellar function in between attacks. There are various types (1–7) and attacks in EA. EA-1 may be triggered by sudden movements, physical and emotional stress, and also by startle.13 Patients may have up to 30 attacks per day. In between these episodes, patients have varying degrees of neuromyotonia1. EA-1 is a potassium channelopathy caused by mutation in KCNA1 gene. The dysfunction of this channel leads to neuronal hyperexcitability. Acetazolamide, a carbonic anhydrase inhibitor, is the drug of choice.3 Overall, EA-2 is the the most common subtype with attacks provoked by exercise, physical and emotional stress. Between the attacks, these patients may be normal or may have nystagmus and mild baseline ataxia.13 The other subtypes are rare with later age of onset (EA-4 and EA-5) and sometimes variable features between the attacks, such as tinnitus, vertigo and diplopia (EA-3), migraine (EA-6). The features in EA-7 are similar to EA-2 but without the clinical findings seen between the attacks.13”
1 Isaacs’ Syndrome “Issacs’ syndrome (also known as neuromyotonia, Isaacs-Mertens syndrome, continuous muscle fiber activity syndrome, and quantal squander syndrome) is a rare neuromuscular disorder caused by hyperexcitability and continuous firing of the peripheral nerve axons that activate muscle fibers” https://www.ninds.nih.gov/health-information/disorders/isaacs-syndrome#:~:text=Issacs’%20syndrome%20(also%20known%20as,axons%20that%20activate%20muscle%20fibers.
Episodic ataxias – “People with episodic ataxia have recurrent episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraine headaches, blurred or double vision, slurred speech, and ringing in the ears (tinnitus)” https://medlineplus.gov/genetics/condition/episodic-ataxia/#:~:text=People%20with%20episodic%20ataxia%20have,in%20the%20ears%20(tinnitus).
Otoneurological Abnormalities in Patients with Friedreich’s Ataxia – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5205522/ “The most evident neurotological symptoms were incoordination of movement, gait disturbances, and dizziness. Alterations in vestibular examinations occurred in 90% of patients, mostly in the caloric test, with a predominance of deficient central vestibular system dysfunction.”
Misdiagnosis of “Very-late-onset Friedreich’s ataxia: diagnosis in a kindred with late-onset cerebellar ataxia” https://pubmed.ncbi.nlm.nih.gov/31467149/ “Friedreich’s ataxia is classically considered a disease with onset in the first or second decade. However, late-onset (age of onset 25-39 years) and very-late-onset (age of onset >40 years) forms do occur rarely. Misdiagnosis is common, particularly because the later onset forms of Friedreich’s ataxia commonly do not show characteristic features of the disorder (areflexia, dysarthria, sensory neuropathy, extensor plantars, amyotrophy, cardiac involvement, diabetes mellitus, scoliosis). Also, there may be atypical features such as spasticity, brisk reflexes and laryngeal dystonia. We present the clinical, imaging and genetic findings of a kindred with very-late-onset Friedreich’s ataxia and discuss the pitfalls and risk of misdiagnosis.”
Ataxia – https://www.mayoclinic.org/diseases-conditions/ataxia/diagnosis-treatment/drc-20355655
“An MRI can sometimes show shrinkage of the cerebellum and other brain structures in people with ataxia. It may also show other treatable findings, such as a blood clot or benign tumor”