Aspecte de psihopatologie în contextul sclerozei multiple – provocare diagnostică şi terapeutică

 Psychiatric psychopathology in the context of multiple sclerosis – diagnostic and therapeutic challenges

First published: 16 aprilie 2021

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/Psih.64.1.2021.4773


The case report describes a complex clinical context of a 24-year-old patient with multiple hospitalizations in psychiatric hospitals for psychotic symptoms and behavioural disorders associated with neurodegenerative pathology. The nosological classification and the temporal association with the onset of multiple sclerosis were both a clinical and a therapeutic challenge, justifying a dynamic monitoring of the symptoms, using the history of MRI procedures and current investigations for further information.

psychosis, mood lability, multiple sclerosis, cognitive impairment


Cazul prezentat descrie un tablou clinic complex la o pacientă de 24 de ani, cu multiple internări în spitale de psihiatrie pentru simptomatologie psihotică şi tulburări de comportament asociate unei patologii neurodegenerative. Încadrarea nosologică şi asocierea temporală cu debutul sclerozei multiple au constituit o provocare atât clinică, cât şi terapeutică, justificând o monitorizare în dinamică a simptomatologiei, utilizarea istoricului imagistic RMN şi investigaţii curente pentru obţinerea de informaţii.

Case presentation

The patient A.B. (24 years old, female), known with a neuropsychiatric history of multiple decompensations and hospitalizations in the last 12 months, is brought to the emergency room of the “Prof. Dr. Alexandru Obregia” Clinical Psychiatric Hospital by the ambulance and the police, at the request of her family, for a psychopathological symptomatology dominated by psychomotor agitation, bizarre psychotic modified behaviour, unsystematic delusional ideas of persecution, low frustration tolerance, and suicide threats. The patient lives alone in an apartment owned by the family, she is unmarried, a high school graduate, but unable to complete the first year of college after several attempts. The patient had to make great efforts to recover two years of education in one year when she moved to Canada. Family relationships are strained, dominated by verbal aggression and episodes of physical aggression. The patient spends a lot of time on social networks, constantly posting images of herself in various poses, which can be translated as behavioural disinhibition.

According to family reports, the patient experienced a psychotraumatic event at the age of 17 years old, being the victim of a sexual assault. The patient has been a smoker since the age of 14, she drinks coffee, and occasionally consumes alcohol and psychoactive substances.

Personal history

At the age of 21 years old, she was diagnosed with recurrent-remissive multiple sclerosis (RR), stating that the disease began with ocular symptoms (optic neuritis of the right eye), with diplopia, scotomas and pain with eye movements. The patient was treated for a year with interferon and methylprednisolone intravenously (i.v).

The patient refused the recommended treatment, due to multiple side effects, preferring the administration of an alternative treatment of her choice with 50,000 IU of vitamin D3 per day, initially, then the same dose weekly. In this decision, she was supported by her parents, against the medical advice.

Psychiatric history

The first admission to a psychiatric service took place three years ago in Canada, before the diagnosis of the neurological condition, for a suicide attempt in the context of a depressive episode with psychotic elements (“My voices told me to throw myself over the window, that God will hold me in his arms”) for which she received treatment with quetiapine 100 mg/day and escitalopram 10 mg/day, with a good evolution, but she interrupted the treatment after a few months. Before the onset, behavioural changes secondary to traumatic emotional relationships were reported, with dysphoric crises, philosophical and religious preoccupations uncharacteristic for her personality, going as far as conversion to another religion (Muslim).

Two years later, she was hospitalized as an emergency at the “Prof. Dr. Alexandru Obregia” Clinical Hospital of Psychiatry for a psychopathological symptomatology dominated by auditory hallucinations, depressed mood, emotional lability, inappropriate affect towards the father and social withdrawal. She received treatment with olanzapine 5 mg/day, escitalopram 10 mg/day and gabapentin 300 mg/day, with the incomplete remission of symptoms.

She was re-hospitalized after seven months for psychomotor anxiety, bizarre psychotic behaviour modification, ideoverbal dissociation, persecutory delusion, ideas of reference, affective ambivalence and inappropriate affect towards the family, irascibility and irritability. She received treatment with olanzapine 7.5 mg/day with the same nonadherence at home, being required to be readmitted three weeks after her discharge from the hospital.

Somatic examination

The medical assessment reveals a BMI of 16.9, with vital signs within normal limits and no motor deficits at the time of admission. On the dorsal side of the hands, bilaterally, the skin has erythematous and scratchy lesions secondary to excessive use of disinfectants and due to dehydration.

Mental status assessment

The patient is time/place/person oriented; the physician-patient contact is relatively difficult to achieve due to the patient’s hostility towards certain subjects and her fear of a negative evaluation, and the visual contact is made and maintained during the course of the interview. The facial expressiveness is in accordance with the verbal and affective content transmitted, with theatrical, demonstrative and artificial notes. No perceptual disturbances like hallucinations are noted at the time of examination. Selective hyperprosexia for hypochondriac themes and focused on the dysfunctional relationship with her father, along with spontaneous hypoprosexia, moderate-severe hypo­mnesia with the inability to complete complex tasks, hypermnesia for certain thematic evocations with psychotic content. In the sphere of thinking, there is a slightly accelerated rhythm of ideas, with the main interest reduced to a few topics aimed towards health, the obsessive aspect of her body shape, preoccupation with evil religious symbols, and suspiciousness. In terms of thinking impairments, there are delusional ideas of persecution, prejudice, reference and with mystical characteristics. Spontaneous speech is present, circumstantiality used to conceal deficit, with a tendency to disorganize under the action of minor stress and lack of cause-effect relationship in the patient’s explanations. The patient’s way of thinking is dominated by distractibility, illogical statements and tangentiality. The verbal rhythm is uneven, with periods of acceleration and verbal outbursts, alternating with periods of mental depletion, lack of concentration and verbal stereotypes. The mood is dysphoric, the patient is short-tempered, has inappropriate feelings towards her father, emotional lability, demonstrative behaviour, aggressive outbursts, rapid action without deliberation and by that sacrificing critical thinking, impulsivity, irritability, social withdrawal, reduced level  of activity, lack of interests, odd way of acting (she shaved the hair in the frontal region to lengthen the oval of her face, she colored the sides of her neck with black eyeshadow to thin her neck appearance, she asked for paper bags to constantly carry makeup, cigarettes and disinfectants). Self-esteem is inflated, she establishes superficial relationships with others, she has erotic disinhibition, suggestibility, motivational ambivalence,  lowered ability to make decisions or to act (hypobulia), apathy, reduced planning of her future, lack of organization, activity sequencing, and reduced abstract thinking. She avoids oral treatment by trying to disguise the administration methods (pills); food instinct and conservation instinct are decreased.

Paraclinical examinations

  • ECG: normal.

  • MDT-dip card toxicology: negative.

  • HCG pregnancy test: negative

  • Total serum vitamin D: 215.84 ng/ml (optimal: 30-100 ng/ml).

  • Biochemistry: within normal limits; normal complete blood count; FT3, FT4, TSH: within normal limits.

  • Ag HBs negative, anti-HCV negative.

  • Urinalysis within normal limits.

Medical imaging

Cerebral and cervical vertebra-medullary contrast-enhanced MRI i.v. 3T, performed in 2017, reveals multiple infracentimetric lesions located at the following levels: right cerebellar, subcortical, bilateral periventricular, parieto-occipital subcortical left, frontal left, and a lesion of 9.4 mm in the posterolateral cords C3 segment, non-gadolinium enhancing lesions and demyelination areas at the right optic nerve.

Contrast-enhanced brain MRI i.v., performed in 2019, reveals areas of demyelination in the brain stem and in the left cerebellar hemisphere, non-gadolinium enhancing lesions, along with multiple bilateral and periventricular demyelination areas in the white matter of the cerebral hemispheres, as well as subcortical lesions, one of 16 mm in the right parietal level and one of 5.6 mm in the left periventricular parietal level.

During hospitalization, the patient complained of diplopia, postural instability, and tremor of the upper limbs. The neurological exam revealed exacerbated deep tendon reflexes in the left hemibody with positive left Hoffmann reflex, suggestive of a lesion in the corticospinal tract.

I.v. contrast-enhanced brain MRI, performed during the current hospitalization, reveals multiple demyelinating processes with similar distribution to the previous example in 2019 sub- and supratentorial, predominantly periventricular and at the cortico-subcortical junction, affecting both edges of the corpus callosum. Lesions in the dentate nucleus and middle cerebellar peduncles, with lesions in the brainstem at the origin of the right V-VII nerves. Multiple bilateral frontal subcortical lacunar lesions.

The psychological examination highlights affective and behavioural disorders, with affective instability, irritability, disproportionate irascibility to the importance of psychosocial precipitating factor, marked apathy, suspicion, paranoid interpretation, severe attention deficit disorder, and short-term memory disorders with altered solving of complex tasks.

Diagnosis motivation

Based on the anamnesis, the symptomatology, the history of the disease, the examination of the mental state (bizarre preoccupations, interrogative-investigative disposition, tendencies to disorganized thinking, social withdrawal, difficulties in maintaining stable interpersonal relationships) and the paraclinical investigations, the supported diagnosis is: organic personality disorder, mixed type (labile and paranoid); psychotic disorder due to multiple sclerosis, with delusional ideas; mild neurocognitive disorder (in research criteria according to DSM IV-TR, but implemented in DSM-5).

Sustained diagnosis

For organic personality disorder, mixed type: persistent personality disorder (marked affective lability, delusional ideas of persecution, prejudice, reference), representing a change in the previous personality pattern; there is evidence that the disorder is the direct pathophysiological consequence of a medical condition – multiple sclerosis (history of brain damage, absence of insight of the phenomenology as attributed to the medical condition, temporal association with the onset or exacerbation of the medical condition); the disorder does not manifest itself exclusively during a delirium; the disorder causes clinically significant discomfort and dysfunction in the social and professional life.

For psychotic disorder due to multiple sclerosis, with delusional ideas: prominent delusional ideas; there is evidence that the disorder is the direct pathophysiological consequence of a medical condition (multiple sclerosis), the disorder does not manifest itself exclusively during delirium, the disorder causes significant clinical discomfort and dysfunction in the social and professional fields, the disorder is not better explained by another mental disorder (affective disorder with psychotic elements or endogenous psychotic disorder), the symptoms evolving in close correlation with the evolution of the neurological disease(1,2).

For the mild neurocognitive disorder, secondary to a medical condition: the patient’s complex attention is affected in such a way that she needs more time than before in order to carry out her usual tasks; an increased effort is required for performing multiple-stage extensive projects, such as the faculty; she mentioned being tired, as a result of the effort needed for organizing, planning or decision making; the learning and memory function was affected (the patient has got difficulties in remembering the recent events and she asks for pen and paper for making lists of products needed for her personal care); she has significant difficulties in finding her words; in this case, the impact on her social resilience appears under the form of decreased empathy, the increase of the introvert behaviour, reduced inhibition and apathy, withdrawal and social disregard(2).

Differential diagnosis

  • Other mental disorders, secondary to a medical condition – the impairment could not be better explained by any other mental disorder, caused by the medical condition(2).

  • Substance or medicine-induced psychotic disorder: the change of personality appears neither in the context of psychoactive substance or consumption, nor in the context of the treatment with corticosteroids(2).

  • The affective disorder with psychotic features or endogenous psychotic disorder – the presence of the etiopathological factor (multiple sclerosis).

  • Other personality disorders – a clinically significant change is present, as compared to the main personality(2), in the evolutive context of the cerebral demyelination lesions.

Present treatment

Due to her unpredictability, her disorganized behaviour and her hetero- and autoaggressive potential, the patient was not voluntarily admitted in the hospital, in compliance with the Law no. 487/2002. The main objectives consisted in improving the delirious symptomatology, as well as proper feeding and hydrating needed for preventing weight loss and the other potential hydroelectrolytic and protein caloric imbalances.

The pharmacological treatment consisted in prescribing antipsychotics, such as zuclopenthixol 1 vial. i.m., three doses; the reason was the noncompliance with the oral medication and the need to eliminate the conceptual-behavioural disorganization, the agitation and the delirious ideas; at a later stage, the treatment with olanzapine 10 mg/day and amisulpride 200 mg/day was started, but the latter was interrupted, due to the induced hyperprolactinaemia (288 ng/mL), mood stabilizer with pregabalin 225 mg/day, vitamins and hydroelectrolytical rebalancing.


Throughout the admission period of 39 days, the evolution was slightly favourable, the patient becoming cooperative and adherent to the therapeutic plan. A significant improvement of the delirious picture, present upon admission into hospital, was noted; however, there were a reduced persistence of the stereotypes, steril behaviour and cognitive deterioration.


Considering the remissive status of the present neurological condition, of the partial insight on the psychotic changes and the experiencing of the dysphoric mood, with explosive behaviour, the prognosis is favourable in the short term. However, the prognosis is unfavourable in the long term, based on the history of treatment noncompliance for both conditions, the precarious emotional support, due to the family conflicts, the disruption of the patient’s social interests, the unpredictability of the multiple sclerosis evolution and the association of the frontally localized ischemic vascular lesions (frontal dysexecutive syndrome). Another factor of negative prognosis is the suicidal risk, the multiple sclerosis being associated with a suicide risk twice as high as in the general population, especially for those in which the disease appears under 30 years old(3,4); the patient already had an attempt in her past record.


The appearance of the psychotic episodes within the context of multiple sclerosis is documented in the specialty literature. The question is whether an endogenous or exogenous organic cause may be the basis of this change of personality structure and the emergence of the psychotic episode. Considering the multiple lesions and their localization at the cerebral and cerebellar levels, we believe that these lesions may be the basis of the delirious ideation of persecution, self-overevaluation, passive behaviour, lack of criticism etc. According to the studies performed until now, around 25% of the patients diagnosed with multiple sclerosis were admitted within the psychiatric service (ambulatory or hospital), at the time or after the beginning of the neurological symptomatology(5).

The possibility of a psychotic episode occurrence in the case of patients suffering from multiple sclerosis is three times higher than in the case of the general population(6). A study made on a lot of 10,000 patients suffering from multiple sclerosis has shown the appearance of at least one psychotic episode in 4% of them(7).

Sixty percent of the patients suffering from multiple sclerosis and psychotic episodes have frontotemporal lesions. Among the patients suffering from multiple sclerosis and a severe psychotic episode, 87% have delirious ideation of persecution, 80% have lack of fear, and 53% have reference ideas. The presence of periventricular lesions can be at the basis of the psychotic episode(8).

When the demyelinising process is affecting the temporal lobe and the diencephalic regions, memory imbalances may appear. These have a prevalence of 40-60% of the patients and the characteristic feature is the fact that the short-term memory is affected. About 50% of the patients have moderate cognitive disorders, which are apparently not linked to the severity of the neurological symptoms or the duration of disease evolution. The depressive episodes are more common than the euphoric or hypomanic states (25-50% compared to 10%), thus explaining the increased suicidal risk. Personality disorders are frequent in the context of multiple sclerosis, therefore 40% of the patients are affected by changes related mainly to irritability and social withdrawal(5).


The diagnosis of organic mental disorder involves a process which is often difficult; on one side, a skilful use of the sequentially performed psychiatric interview is needed, both with the patient, and with the people who might provide credible information. On the other hand, a thorough psychological examination is also needed, for covering both the cognitive and the affective-relational sides of the personality, and also a targeted dynamic psychopharmacologic interventions. These are completed by complementary paraclinical checkups, used to certify the correlation between the organicity and the psychiatric symptomatology(9).


  1. DSM IV-TR. Manual de diagnostic şi statistică a tulburărilor mintale, ediţia a patra revizuită, Bucuresti, 2003, Asociaţia Psihiatrilor Liberi din România p.188-190; 334-338; 764.
  2. DSM-5. Manual de Diagnostic şi Clasificare Statistică a Tulburărilor Mintale, American Psychiatric Association, Editura Callisto, 2016, p593-595,645, 707.
  3. Brønnum-Hansen H, Stenager E, Nylev Stenager E, et al Suicide among Danes with multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry. 2005;76:1457-1459.
  4. Sadock BJ, Sadock VA, Pedro Ruiz P. Kaplan & Sadock’s synopsis of psychiatry: behavioral sciences/clinical psychiatry. 11th ed. Philadelphia: Lippincott Williams & Wilkins, 2015; p. 720, 728.
  5. Stenager EN, Stenager E, Koch-Henriksen N, Brønnum-Hansen H, Hyllested K, Jensen K, Bille-Brahe U. Suicide and multiple sclerosis: an epidemiological investigation. J Neurol Neurosurg Psychiatry. 1992;55:542-545.  
  6. Gilberthorpe TG, O’Connell KE, Carolan A, et al. The spectrum of psychosis in multiple sclerosis: a clinical case series. Neuropsychiatr Dis Treat. 2017;13:303-318. 
  7. Patten SB, Svenson LW, Metz LM, Psychotic disorders in MS: Population-based evidence of an association. Neurology. 2005 Oct;65 (7):1123-1125.
  8. Camara-Lemarroy CR, Ibarra-Yruegas BE, Rodriguez-Gutierrez R, Berrios-Morales I, Ionete C, Riskind P. The varieties of psychosis in multiple sclerosis: A systematic review of cases. Multiple Sclerosis and Related Disorders. 2017 Feb;12:9-14.
  9. Trifu S, Marian G, Uţă A. Tulburarea organică de personalitate – aspecte clinice şi elemente de diagnostic diferenţial. Lucrare prezentată în cadrul celui de-al III-lea Congres dedicat Cercetării Ştiinţifice Psihiatrice din România, Oradea, România, 2013.

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