CME INDIA Case Presentation by Dr. N. K. Singh, Admin.

CME INDIA Case Study

  • A 55-year, non-diabetic female visited on 30th March 2021 with history of typical GERD symptoms and depressive neurosis. The attending physician after evaluating started 1. Rabeprazole(20mg) and Levosulpiride. (75mg) combination 2. Escitalopram and clonazepam (5/0.5) combination. (Thyroid function/USG Abdomen/GIT endoscopy – Normal).
  • Just approximately one month of these medications she started the abnormal movement but came to physician on 24.06.2021 as shown in video.

Usual physical examination is unremarkable except the abnormal movement of oro-mandibular area

  • What is the diagnosis?
  • What investigations now needed?
  • How you will manage this case?

CME INDIA Discussion

Dr Prabhat Agarwal, MD, Agra:

  • Due to Levosulpiride.

Dr Ritesh Chaudhary, Kanpur:

  • Yes, stop Levosulpiride, give trihexyphenidyl – if it doesn’t subside after stopping.

Dr Noni G Singha, MD, Dibrugarh, Assam:

  • Dyskinetic movement.
  • It is also causing menstruation irregularities indirectly in females by causing drug induced hyperprolactinemia.
  • Gradual withdrawal (in few days’ time) of Levosulpiride. Will be better as symptoms may worsen after sudden withdrawal. Now she is 75 mg per day. 50 mg for next 3-4 days, then 25 mg for next 3-4 days and stop.

Dr N K Singh:

  • Why gradual?
  • Dr Noni-In acute onset EPS to drugs one must stop immediately. But cases like this which is chronic (having medicine for 3 months and symptoms for 2 months) there may be chance of worsening of symptoms on sudden withdrawal. Do the gradual withdrawal to avoid that, moreover the symptoms for which she was taking will also be gradually adjusted. Or one may try sudden stoppage also. In Levosulpiride induced dyskinesia I usually taper and stop in one week time. Symptoms may worsen on sudden withdrawal Sir.

Dr S K Goenka, Begusarai:

  • Oromandibular tremor /tardive dyskinesia.

Dr V P Youmash, Assistant professor, KAPV medical college, Trichy, TN:

  • Perioral tremors (rabbit syndrome) drug induced dyskinesia?

Dr B K Singh, MD, Samastipur, Bihar:

  • Levosulpiride induced tar dive dyskinesia oro-lingual type.
  • Prognosis-Usually irreversible even after discontinuation of Levosulpiride.

Dr Kamal Doshi, MD, Rajkot:

  • Levosulpiride induced orolingual dyskinesia. The clinical diagnosis of “LSP-induced dyskinesia” is based on the clinical profile, temporality of the adverse effect with drug intake, plausible explanation based on the pharmacological effects of the drug, outcome following drug dechallenge, and exclusion of other causes.
  • The specific movements involved in orofacial dyskinesia can be one or combination of the following movements, for example, protrusion or twisting of the tongue, smacking and pursing of the lips, puffing of the cheeks, chewing movements of the jaw, and grimacing movements of the face. In few cases, it may be irreversible…
  • Treatment: withdrawal of medicine. Phenergan.

Dr Sangram Biradar, Gulberga:

  • Levosulpiride induced.

Dr S K Gupta, MD(Med) CFM (France), Delhi:

  • Just Stop it, Give Phenergan tab or Diazepam tab.

Dr Gaurabh Gupta, New Delhi:

  • It’s related to levosulpiride, Orofacial mandibular dystonia.

Dr N K Singh:

  • Some say dystonia, some dyskinesia, some say it is irreversible, some say will subside?

Dr Abhishek Kr Singh, DM, Neuro, Patna:

  • Levosulpiride causes very diverse kind of movement disorder. Could be it’s related to that. It’s reversible in most of cases.
  • Stop levosulpiride.
  • Start on Pacitane and lorazepam. It is dyskinesia.

Dr Ritesh Chaudhary, Kanpur:

  • Why drug induced movement disorder will be irreversible? Oro-facial or oro-mandibular dyskinesia is quite frequently seen in clinic after the rampant use of levosulpiride with ppi in GERD.

 Dr Ashok Kumar, DM, Neuro, Ranchi:

  • Looks like Levosulpiride induced Parkinsonism.
  • Parkinsonian tremor – lower jaw and hands (MCP joints) PLUS Upper face Hypomimia.
  • Hand tremor part of video lasts only seconds.
  • Examination for hand tremor, rigidity, Cog- wheeling and Gait should make it clear.
  • STOP Levosulpiride.
  • Anti-cholinergic (THP) should be started.
  • It will take several weeks before it subsides. May be even 2 – 3 months.
  • I have seen 2 cases in last 15 years, where Parkinsonism started as Drug – induced   complication. BUT, turned out to be Parkinson’s disease.
  • A close examination will show that in this lady movements are Lower jaw tremor – side to side. These are regular. Suppressed when the patient speaks. No lip or tongue movements (dyskinesia) can be seen. Also, there is masking of the visible part of upper face. Tremor in hands can be seen. This part of the video should have been longer. A video of gait will be helpful. Drug-induced Parkinsonism takes time to resolve – several weeks.

Dr Sangita Kamath, MD, Jamshedpur:

  • Rabbit syndrome. Stop citalopram, add THP. Tongue spared.

Dr Ashok Kumar, DM, Neuro, Ranchi:

  • In Rabbit syndrome, we see Parkinsonism.
  • Movements are horizontal. Not vertical (Rabbit Syndrome).

(Rabbit syndrome (RS) is characterized by fine, rapid, rhythmic movements along the vertical axis of the mouth. Long-term exposure to the older neuroleptics has clearly been associated with RS, but little is known regarding the risk of RS due to the exposure to the newer atypical antipsychotics. This syndrome is considered a distinct neuroleptic-induced extrapyramidal syndrome. There is evidence that RS combines features of both Parkinson’s disease and tardive dyskinesia).

Dr Ujjawal Roy, DM, Neuro, Ranchi:

CME INDIA Learning Points

  • Levosulpiride is currently being increasingly used for various gastrointestinal disorders such as irritable bowel syndrome, gastroesophageal reflux disorder, nonulcer dyspepsia, and as a prokinetic agent.
  • Fixed dose combination (FDC) products of LSP with proton-pump inhibitors (PPIs) are being prescribed in India and needless to say, its use is rampant.
  • Levosulpiride frequently causes drug-induced movement disorders, presenting mainly with Levosulpride induces Parkinsonism(LIP) followed by lower face dyskinesia.
  • The symptoms are often severe, and usually reversible. But it could be irreversible even after the withdrawal of levosulpiride.
  • Physicians should be cautious in using levosulpiride, especially in elderly patients.
  • D2 receptor antagonists (antipsychotic drugs) are known to cause extrapyramidal syndrome (EPS) that includes acute muscular dystonia, neuroleptic malignant syndrome, dyskinesia, and Parkinson’s disease. One of such kinds of drug is LSP with additional serotonin receptor affinity.
  • Levosulpiride is exerts its pharmacologic activity mainly by blocking dopaminergic D2 receptors.
  • The specific movements involved in orofacial dyskinesia can be one or combination of the following movements, for example, protrusion or twisting of the tongue, smacking and pursing of the lips, puffing of the cheeks, chewing movements of the jaw, and grimacing movements of the face. Whereas, limb and trunk movements include purposeless, jerky, choreiform movements, athetosis of the extremities, limb and axial dystonias, gait abnormalities, lordosis, shoulder shrugging, and rotatory movements of the pelvis.
  • It is well known that combination of PPI and LSP turns out to be effective in the treatment of functional dyspepsia, yet the concerns for safety should limit its prolonged usage.
  • Shin et al found levosulpiride-induced parkinsonism (LIP) (93.4%) to be the most common LIM followed by TD (9.9%) and isolated tremor (3.3%). 85.7% patients were aged above 60 years. The oro-lingual area was the only body part that was involved in case of TD. Levosulpiride-induced TD persisted after withdrawal of levosulpiride in 66.7% patients with dyskinesia tremor.
  • Treatment is based of withdrawing the offending drug and with lonazepam usually.
  • Difference between Dystonia and Dyskinesia
DystoniaDyskinesia
Dystonia is a type of movement disorder which consists of involuntary muscle contractions that may be continued or intermittent in nature.Dyskinesia is a term used for uncontrollable, abnormal and involuntary movements.
These contractions result in twisting movements that are repetitive in nature, abnormal or irregular postures, or maybe both.These movements may be similar to chorea or tics
The existence of abnormal postures that substitute the voluntary movements or superimpose upon them is a typical feature of dystonia.Voluntary movements are diminished in dyskinesia.
The postures in dystonia are repeated.Dyskinesia ranges from a very mild tremor in the extremities to an uncontrollable movement in other parts.
Specific postures or patterns are typical for every child at a given point in time.There might be a loss of coordination internally as well, especially seen with the respiratory muscles. Also, this is generally not recognized.
Postures or patterns may be sustained or there may be a brief interval between two episodesDyskinesia is also a sign or symptom of many medical conditions.
The postures in dystonia usually get triggered when one attempts voluntary movements.These medical conditions are differentiated based on their underlying cause.
In some cases, the postures get triggered only in specific body positions. task-specific dystonia is an example of this.Dyskinesia can be classified into different types like medication induced dyskinesia, chronic or tardive dyskinesia, non-motor dyskinesia.
Except for some seizure conditions, the postures of dystonia are not seen in sleep. This may be due to inhibition of movements due to the action of spinal cord.The symptoms of dyskinesia may begin with minor tics, shakes or tremors. These are usually seen in one’s hand or foot that is dominant.
Postures and patterns can be sustained for different lengths of time.The different types of dyskinesias are connected to different sets of causes.
There may be a lack of relaxation.Most of the times, dyskinesia is treated when the symptoms become severe.
Multiple dystonic patterns or postures may be seen in the same child.Some disorders like autism may also cause dyskinesia. In such cases, behavioral therapy may prove to be useful.
The movements in dystonia are more stereotyped and predictable.Symptoms of dyskinesia usually worsen gradually over a period of time.
The movements in dystonia are less quick or rapid.The symptoms can even increase in intensity or develop suddenly after a brain injury.
Voluntary movements may trigger dystonic movements.The various types of dyskinesia cause various symptoms which help in identifying the type of dyskinesia and help in establishing a treatment protocol.
Dystonia is marked by specific implanted postures and not by implanted movement.The course of treatment for each type of dyskinesia usually depends on what part of brain has been affected.
The most common types of dyskinesia are- Parkinson’s dyskinesia, tremors, dystonia, chorea, tardive or delayed dyskinesia, myoclonus, spasmodic torticollis, ballism, athetosis, stereotypies and tics.
Thus, dystonia can be said to be a type of dyskinesia and that is the difference between the two.

CME INDIA Tail Piece

 Dr Sanjay Gandhi, MD, Pune:

  • What is this? Unilateral rest coarse tremors. Very stressed person.

Dr Anil Kumar, MD (Pshy), Ranchi:

  • Parkinsonian Tremors.

Dr Ashok kumar,DM ,Neuro,Ranchi says….

It is NOT Parkinsonian tremor .
That is RUBRAL Tremor .
Also called Holmes tremor .

What you think,please comment

References:

  1. Danion JM, Rein W, Fleurot O. Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Amisulpride study group. Am J Psychiatry. 1999;156:610–6. 
  2. Gupta S, Garg GR, Halder S, Sharma KK. Levosulpiride: A review. Delhi Psy J. 2007;10:144–6. 
  3. Shin HW, Kim MJ, Kim JS, Lee MC, Chung SJ. Levosulpiride induced movement disorders. Mov Disord. 2009;24:2249-53.
  4. Thomas R, et al. Levosulpride induced involuntary movements. Indian Journal of Gastroenterology 37 (Suppl. 1): A130-A131 abstr. 428, Oct 2018. Available from: URL: http://doi.org/10.1007/s12664-018-0911-4 [abstract] – India


Discover CME INDIA:

Discover CME INDIA