Symptoms of multiple sclerosis: Paroxysmal symptoms

paroxysm /ˈperəkˌsɪzəm/ noun plural paroxysms Britannica Dictionary definition of PAROXYSM medical: a sudden attack or increase of symptoms of a disease (such as pain, coughing, shaking, etc.) that often occurs again and again — usually + of paroxysms of pain/coughing formal: a sudden strong feeling or expression of emotion that cannot be controlled a paroxysm of rage He went into paroxysms of laughter. What are Paroxysmal symptoms? Paroxysmal symptoms (PS) refer to a sudden onset of a neurological symptom, or cluster of symptoms that may last over seconds to minutes, repeating a few to very many intervals per day. They are well-recognized manifestations of multiple sclerosis (MS), and manifest as motor, sensory, visual, brainstem, and autonomic symptoms. When occurring in the setting of an established MS, the diagnosis is relatively straightforward. Conversely, the diagnosis is significantly more challenging when they occur as the initial manifestation of MS. They are considered relapses when occurring over no less than 24 h. PS have a reported incidence of 1.6% to 17% in patients with MS during their disease course of which 24% occur as the initial manifestations of the disease. Although PS are classically described in relapsing remitting MS, some types have been also described in the setting of progressive MS. Although PS are not uncommon, they remain underrecognized and pose a diagnostic challenge, leading to a delay in the initial diagnosis of MS, failure to recognize signs of a relapse in patients with an established MS, and thus deferring initiation of adequate treatments. PS need to be differentiated from other paroxysmal events occurring in the setting of MS such as comorbid migraine, seizures, and sleep disorders. In addition, transient worsening of pre-existing deficits due to extrinsic factors such as fever and fatigue, the so-called Uhthoff’s phenomenon, are not considered PS. What causes Paroxysmal symptoms: The reasons for PS remain incompletely understood. However, several mechanisms have been proposed to explain this phenomenon. The most popular theory was proposed by Osterman et al. whereby partially demyelinated axons favor the ectopic generation of spontaneous nerve impulses which transversely spread (ephaptic transmission) to other axons within the fiber tracts ultimately manifesting as paroxysmal attacks. This hypothesis is supported by the fact that proprioceptive and tactile stimuli are well established triggers of certain types of PS. On the other hand, the role of “inflammatory irritation” has been proposed based on the favorable response to steroids in many reported cases. Yet, another possible mechanism is ion channel dysfunction in partially demyelinated axons. Such changes would render the axons hypersensitive to minor physiological changes, such as low ionized calcium secondary to hyperventilation, a known trigger of PS. This theory is also supported by the dramatic effect of acetazolamide and anti-epileptics on the frequency of attacks. These theories remain purely speculative and it is not excluded that a combination of the aforementioned factors, and possibly some other unknown phenomena, ultimately result in the generation of PS. What can be done if an MS patient experiences paroxysmal symptoms: If you are aware of any triggers for your paroxysmal symptoms, such as making a particular movement or getting too hot, you could try to avoid these. Keeping a symptom diary can be helpful for identifying triggers that you may not be aware of. Paroxysmal symptoms categories Motor symptoms: 1. Paroxysmal Dyskinesia: is a group of hyperkinetic movement disorders characterized by recurrent episodes of dystonia, chorea, athetosis, or a combination of the latter. Paroxysmal dystonia (PD) is the 2nd most commonly described movement disorder in MS after tremors. Also known as tonic spasms, these episodes consist of abrupt onset, stereotyped involuntary dystonic posturing. PD can be categorized into painful vs. painless, kinesigenic vs. non-kinesigenic, and generalized vs. focal. Generalized dystonia is described as an episode of unilateral upper limb flexion and lower limb extension with a potential to spread to the neck or face. Preceded by sensory aura. Associated with pathological laughter or autonomic symptoms. Treatment: Pulse steroid therapy alone or combined with antiepileptics or antiepileptics alone. Focal forms include: Oromandibular dystonia: mouth opening , deviation of the jaw and lips or tongue protrusion. Can lead to speech and swallowing problems. Treatment: Trihexyphenidyl hydrochloride. pharyngeal dystonia: Transient painful dysphagia associated with abnormal sensation in the throat . Treatment : Carbamazepine Hand dystonia (writer’s cramp) These episodes are often precipitated by movement, hyperventilation, and physical or emotional stressors. They last for less than 1 min, and tend to gradually increase in frequency over time, reaching up to 100 times per day. Commonly misdiagnosed as focal onset seizures, a normal electroencephalogram (EEG) during the event points towards the non-epileptic origin of these movements. Most of the patients responded within few hours to days of starting medications for treatment , and were able to successfully stop them after a month with no residual symptoms. On the other hand, paroxysmal choreoathetosis (PC) are described as non-rhythmic flowing and twisting movements of one or more limbs. PC share similar characteristics as PD with comparable duration, frequency, and precipitating factors. Myokymia and Hemifacial Spasms: Myokymia is defined as vermicular muscle twitching, most commonly involving the orbicularis oculi muscles. In MS, facial myokymia (FM) may progress into non-sustained contractures (hemifacial spasms, HFS), sustained contractures (paretic hemifacial contracture), or lower motor neuron type facial palsy. Alternatively, it can resolve spontaneously. A persistent (more than 6 months) or progressive FM should raise suspicion of secondary causes including MS. Additionally, the pattern of muscle involvement in patients with HFS can differentiate between idiopathic and secondary HSF. Most patients with idiopathic HFS initially have contractions of periocular muscles alone, that later spread to the orbicularis oris and finally the platysma muscle. Conversely, patients with secondary HFS have involvement of the upper and lower facial muscles simultaneously, including the platysma muscle. MRI findings are consistent with ipsilateral lesions in the post-nuclear, postgenu portion of the facial nerve, located in the pons. Most patients in studies had resolution of their symptoms with steroid , gabapentin, or carbamazepine. Botulinum toxinshowed results too. Tourettism : is characterized by involuntary motor and phonic tics secondary to neurological and psychiatric disorders. Only a few cases of tics in MS patients have been published. The first patient had a simple phonic tic presenting as paroxysmal throat clearing sounds that were reduced after initiation of pimozide. he second patient with secondary progressive MS was treated with quetiapine for Tourette-like symptoms with vocal tics, stereotyped movements, and coprolalia. The third patient reported decreased vocalization of the phonic tics after administration of dronabinol. All three patients had demyelinating lesions in the basal ganglia and/or thalami. Paroxysmal Weakness (PW):has been reported under several names such as paroxysmal motor symptoms, paroxysmal akinesia, and paroxysmal loss of use. Paroxysmal weakness (PW) bears many points of resemblance to other paroxysmal symptoms in the duration, frequency, precipitating factors and treatment options. Patients have described their weakness as “heaviness”, “knee locking”, “leg giving away”, “unexpected falls”, and “objects dropping out of hands” depending on which limbs are involved in the attack. Occasionally, these motor episodes are associated with concomitant symptoms. Examples include blurred vision, dizziness, paresthesia, pathological laughter, and urinary incontinence. Although these episodes can be initially mistaken for transient ischemic attack, an MRI in favor of MS should suggest otherwise. The appearance of the acute lesion can lend further support to the diagnosis of MS. A rare form of generalized PW is cataplexy (Sudden collapse without loss of consciousness). In addition to be a symptom of narcolepsy, a comorbid condition with MS, cataplexy has been described as a paroxysmal symptom in MS patients with lesions affecting the hypothalamus or reticular activating system (i.e., within the pons and midbrain). Treatment with clomipramine was used to control cataplectic attacks in one patient. Sensory Symptoms: Dysesthesia is the generic term used to describe unpleasant cutaneous symptoms such as burning, tingling, anesthesia, itching, tickling, and pain without any primary skin condition. Some of the major types of dysesthesias are: Lhermitte’s sign (LS): Electric-like sensation felt at the back of the neck following neck flexion. Most MS patients cope well with this symptom, when problematic, neck braces/collars have been used to decrease neck movements that provoke LS. Carbamazepine had an immediate symptomatic effect in 3 patients with LS. In addition, extracranial picotesla range pulsed electromagnetic fields was found to be effective. Paroxysmal Pruritus: Intense itch with a dermatomal distribution. Often occurs during sleep. Paroxysmal pruritus may occur in isolation or can be a predictive symptom immediately before an exacerbation or occur in the recovery phase of a sensory or motor attack. Carbamazepine was the treatment of choice in all patients with phenytoin, phenobarbital and synacthen used as alternatives. However, it is worth noting that these findings should be interpreted with caution since, at the time of these reports, patients were not tested for the presence of NMOSD-specific antibodies (i.e., anti-aquaporin-4 IgG) since the latter were not known widely. Paroxysmal pelvic pain: A rare manifestation of MS, but important to note. Characterized by Lancinating pain radiating to the perianal area. Triggered by change in position. Anti-epileptics are the mainstream treatments. Trigeminal neuralgia (TN) : Shock-like pain in one or more divisions of the trigeminal nerve. Compared to patients with primary TN, TN secondary to MS occurs at a younger age, has a lower frequency of ophthalmic division involvement, higher frequency of bilateral trigeminal nerve involvement, and higher incidence of sensory deficit. Treatment options can be categorized into pharmacological, neuromodulation and surgical treatments. Glossopharyngeal neuralgia (GN) : Characterized by recurring attacks of severe pain in the back of the throat, radiating to the ear or jaw. Associated with salivation, coughing, hoarseness and syncope. Treatment options can be categorized into pharmacological, neuromodulation and surgical treatments. Occipital neuralgia (ON): Unilateral episodic shooting pain in the distribution of the occipital nerve, mostly in patients with lesions involving the C2-C3 cervical spine. GN and ON are treated in the same manner as TN, although evidence to support this approach is lacking. Sciatica: Pain radiating to the back of the leg. Features differentiating it from sciatica caused by compression of the sciatic nerve include early age of onset, absence of improvement with rest or anti-inflammatory drugs, and absence of mechanical triggers. Brainstem- or Cerebellum-related disorders Autonomic symptoms: Autonomic dysfunction is a prevalent and significant cause of disability among MS patients. The spectrum of disorders ranges from cardiovascular dysfunction, bladder, bowel, and sexual symptoms to thermoregulatory dysfunction. Most MS patients with symptomatic autonomic dysregulation typically have a long history of MS and are significantly disabled (high Expanded Disability Status Scale score). This should be distinguished from paroxysmal autonomic disorders occurring in the setting of an MS relapse. Paroxysmal atrial fibrillation (PAF): Can rarely occur in the context of an acute brainstem relapse. Associated symptoms include vertigo, headache, diplopia, and ataxia. MRI demonstrated multiple areas of demyelination involving the brainstem in the reported cases, presumably affecting the ambiguous and afferent solitary nuclei. PAF episodes were treated with the same medications used to abort cardiac atrial fibrillation. Orthostatic hypotension: Syncope upon standing. The orthostatic drop in blood pressure was of sufficient magnitude to cause recurrent syncope. The culprit lesion was identified in the paramedian tegmentum and base of medulla. Pulse steroids therapy and L-threo-3,4-dihydroxyphenylserine caused regression of the other brainstem signs and reduced syncopal attacks. Urinary incontinence: Patient with MS exhibit diverse manifestations of lower urinary tract dysfunction ranging from detrusor overactivity to detrusor areflexia. These manifestations follow the same natural history of MS course. Urinary symptoms have been reported as paroxysmal, in conjunction with other paroxysmal symptoms. Paroxysmal diplopia: Can be horizontal or vertical in nature depending on the underlying cause. Intermittent horizontal diplopia can be the result of recurrent episodes of bilateral eye adduction coupled with miosis. Treatments with reported benefits include steroids, carbamazepine, bromocriptine or cycloplegia Visual-evoked nausea and vomiting: Nausea and vomiting triggered by movement in the visual field. A possible explanation for the visual-evoked paroxysmal nausea and vomiting (PNV) are lesions affecting the efferent connections between the visual cortex and the pontine/medullary reticular formation. Patients with PNV found relief after pulse steroid therapy and after eye closure. Patients with PNV found relief after pulse steroid therapy and after eye closure. Central position vertigo (CPV): Recurrent positional vertigo. Associated with atypical nystagmus pattern. Poor response of Dix-Hallpike maneuver. Hemiataxia and crossed paresthesia: Hemiataxia preceded by contralateral facial paresthesia Ataxia with ocular flutter: Incoordination of the limbs + gait ataxia + visual blurring Dysarthria and ataxia: Starts with dysarthria followed by gait ataxia. Followed by ipsilateral sensory symptoms. There is no evidence-based approach on how to treat MS patients with paroxysmal ataxia and the effectiveness of various treatments is based on case reports. Standard antiepileptics such as carbamazepine, levetiracetam, lamotrigine, and phenytoin were found to be effective in aborting ataxic episodes. Dysarthria without ataxia: Slurred speech. Associated with jaw tension, facial numbness, and handwriting difficulties. Reported cases were firstly treated with intravenous steroid therapy in combination or followed by carbamazepine. Lamotrigine abolished attacks two weeks after initiation in a case resistant to carbamazepine Breathing symptoms: Respiratory problems mostly happen more advanced MS, nut could be seen in earlier stages of the disease course with brainstem relapse . eg: Hyperventilation that is precipitated by sudden movements or exercise, and paroxysmal apneustic Unlike hyperventilation, apneustic episodes were triggered by deep breathing, emotional stress, and swallowing. These attacks are for the most part self-limiting. Cough: paroxysmal cough in young patients who have all the workshop for all respiratory and gastrointestinal problems negative, should be screened for neurological origins of cough , including MS. Cough can be presented by tingling in the throat ( preceding by aura) , and is unresponsive to antitussive medications . These cough attacks were greatly improved by anti-epileptic medications e.g. carbamazepine and valproate sodium. Hiccups: with or without vomiting were rarely described in MS. Could be accompanied by Syncope or other neurological symptoms. It is worth mentioning that paroxysmal symptoms are typically common but underrecognized and oftentimes misdiagnosed. Just because they are intermittent, doesn’t mean they are less important. A lot remains unknown about these symptoms. Treatment paradigms are mostly based on expert opinions and case series rather than high quality supportive evidence, and may only be used for a few weeks or months to control the symptoms but then the dose may be decreased or stopped to see if patients are now symptom-free. Until then, awareness among neurologists of these unusual symptoms will help avoid unnecessary diagnostic delays. To be continued… https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600828/ https://pubmed.ncbi.nlm.nih.gov/1148814/ https://pubmed.ncbi.nlm.nih.gov/13927536/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC493514/ https://pubmed.ncbi.nlm.nih.gov/23522528/ https://pubmed.ncbi.nlm.nih.gov/19695578/ https://pubmed.ncbi.nlm.nih.gov/12474993/ https://pubmed.ncbi.nlm.nih.gov/18496477/ https://pubmed.ncbi.nlm.nih.gov/7373330/ https://pubmed.ncbi.nlm.nih.gov/8869424/ https://pubmed.ncbi.nlm.nih.gov/15589308/ https://pubmed.ncbi.nlm.nih.gov/22130044/ https://pubmed.ncbi.nlm.nih.gov/30782116/ https://pubmed.ncbi.nlm.nih.gov/3004282/ https://pubmed.ncbi.nlm.nih.gov/7673977/ https://pubmed.ncbi.nlm.nih.gov/21264473/ https://pubmed.ncbi.nlm.nih.gov/3925448/ https://mssociety.ca/about-ms/symptoms#:~:text=Paroxysmal%20Symptoms&text=They%20may%20include%20(but%20are,sensory%20disturbance%2C%20and%20Lhermitte's%20sign.&text=Management%20includes%20ruling%20out%20non%20MS%20causes%20of%20paroxysmal%20phenomena. https://www.mstrust.org.uk/a-z/paroxysmal-symptoms