3.4. Co-prescribed drugs
Antipsychotics use was reported in half of the cases (n=61, 49.6%).
First-generation antipsychotics were used in most cases (n=58, 95.1%),
the most frequently reported being haloperidol (n=30), chlorpromazine
(n=16), thioridazine (n=4) and fluphenazine (n=4). Four patients used
second-generation antipsychotics (olanzapine n=3 and quetiapine n=1).
Other reported psychotropic and non-psychotropic treatments are detailed
in Table 1. The most frequently reported were antidepressants (n=14),
anticonvulsants (n=10) and benzodiazepines (n=8).
3.5. Associated medical
conditions
Fever and/or infection was reported in nearly half of the patients
(n=59, 48%). Information on the presence of fever was absent in 9
patients with infection. The most frequent infection was pneumonia
(n=12) [25, 29, 34, 40-45]. Probable or definite neuroleptic
malignant syndrome was observed in 6 patients [22, 28, 35, 36, 46,
47], and heat stroke in one patient [23]. The other medical
conditions (anorexia, surgery, dehydration, chronic kidney disease,
alcohol use, etc.) are described in Table 1.
3.6. Type of neurological
sequelae
Cerebellar sequelae were reported in most cases (n=97, 78.9%) and were
the only neurological syndrome in 58 cases (60.4% of those with
cerebellar symptoms). The other frequently reported neurological
sequelae were cognitive deficits/dementia (n=17, 13.8%),
choreoathetosis (n=12, 9.8%), parkinsonism (n=11, 8.9%), dyskinesia
(n=9, 7.3%) and peripheral neuropathy (n=7, 5.7%). Other rare sequelae
are described in Table 1.
3.7. Characteristics associated with
occurrence of cerebellar
sequelae
Multivariate analyses were performed in the sample of cases without
missing data on the variables of interest (n=109, 88.6%). Two
characteristics were independently associated with the occurrence of
cerebellar sequelae (Table 2): plasma lithium level ≥ 2.5 mEq/l
(moderate/severe toxicity) and (ii) presence of fever and/or infection.
An association was found at trend level between age and type of
sequelae, the proportion of patients aged 50 years and over being higher
in the group with cerebellar sequelae. No association was found between
type of sequelae and gender or antipsychotic use.
To further explore whether the impact of fever on the occurrence of
cerebellar sequelae was modified by lithium plasma level, the
interaction term “fever*lithium level” was entered in the multivariate
model. As this interaction was significant (Wald test Chi2=6.31,
p=0.01), we performed analyses stratified by maximum lithium plasma
levels. This showed that the association between fever and/or infection
and cerebellar sequelae was strong (OR=13.9, 95%CI 3.21-60.05) in cases
with no/ mild lithium toxicity, while it was not significant in those
with moderate/severe lithium toxicity (OR=0.92; 95%CI 0.12-7.10).
Sensitivity analyses using the variable “strictly defined fever”
(i.e. cases with reported
information on this symptom) showed comparable associations between
fever and cerebellar sequelae: 40 (47.1%) patients with cerebellar
sequelae had a history of fever vs. 4 (16.7%) of patients with other
sequelae (OR=5.65, 95%CI 1.65-19.37, p=0.006).