J Med Cases

Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc

Journal website https://www.journalmc.org

Case Report

Volume 15, Number 8, August 2024, pages 195-200

Methylphenidate for the Treatment of Post-COVID Cognitive Dysfunction (Brain Fog)

**Table 1.** Qualitative Visit Notes on Pre-/Post-Psychostimulant Drug
Subject	Pre-drug	Post-drug
1	Patient described problems with word finding and slow speed of processing. Symptoms better in the morning and get worse in the afternoon as the day goes on. patient is an attorney and writes all day for work. Also has some troubles conversing and preparing for any kind of legal argument. Patient also described troubles with short-term memory and repeating themself. Had to keep lists in personal life, but not so much in his work life. Finds that brain fog comes and goes particularly alongside their physical condition. For example, if they are physically fatigued.	Patient continued to complain of problems with concentration and sustained attention as well as fatigue. Patient did not respond well to Ritalin and went back on modafinil (200 mg). Medication stopped; patient returned to new “normal” baseline.
2	Patient reported dyspnea on exertion, easy fatigability, and difficulties with memory and concentration. Finds that when having a conversation thy often forget what their partner said. Patient’s partner had noticed this and is the reason they came to the COVID clinic. Subjective memory complaints which impair the patient occupationally, but remarkably patient was quite normal on formal neuropsychologic testing.	Patient had been taking Ritalin currently 5 mg with breakfast and lunch did not notice any benefit nor any side effects at this time. At the beginning patient reported having headaches for a few days but they went away. Patient reported that they do not notice that Ritalin has significantly affected cognition for the better, nor any adverse events. Patient did not notice any benefit nor any significant adverse events from low-dose Ritalin and the dose increase the dose to 10 mg twice daily. Patient developed slight stuttering and poor appetite after the dose increase. However, he did not notice any improvement in his brain fog or concentration and methylphenidate was stopped.
3	Severe case of COVID-19, had collapsed lung and pneumonia. Patient reported problems with memory, concentration and also possible language. Unable to read or write for a several months following COVID-19 infection. Difficulty writing. Cannot keep track of the day or what they are doing. Sometimes they lose track of whole days or sections of the day. Easily overstimulated and when overstimulated has a hard time concentrating. Sometimes has to pull over and take a rest while driving to calm their mind down. Has to use their GPS or they will get lost even in their own neighborhood. Describes trouble with sustained attention.	Started patient on methylphenidate (Ritalin) 5 mg in the morning with breakfast and as instructed to increase after 2 weeks to 5 mg with breakfast and lunch (10 mg total). They had a lot of adverse effects and stopped the medicine after approximately 10 days. These adverse effects included nausea, some vomiting, and disturbed sleep. They really tried quite hard to stick with the medicine hopefully go away but they did not. Once stopped the medication, the side effect dissipated in a couple of days and they are back to their normal self. They describe some dissociative symptoms and also problems with retrieving information and concentration.
4	Had mild case of COVID-19 in December 2021. Around March 2022 patient noted that they were not thinking as clearly as they should. Patient describes it “like a heaviness on their brain that slows them down”. Patient described struggling under any “mental or physical exertion”. For example, they feel that the “stress of today’s visit will exhaust them”. Post-COVID complaints of problems with concentration, and some modest deficits on testing (recall and lexical fluency). Patient has had to stop working due to cognitive changes. Patient found they were making mistakes, taking longer to get the same amount of work done, and had to finish up the day at home because they had to double-check everything, they had done at work that day.	Patient reported improved cognitive energy and focus. Patient had a greater ability to complete tasks, used to leave everything pretty much half-done but now not as much. However, patient reported notable ups and downs, the downs he refers to as “crashes”. Some of them seemed related to medication wearing off, i.e., getting cognitively fatigued at around 3 p.m. This was not a consistent symptom. Patient reported no adverse effects: Ritalin hasn’t affected sleep or appetite, or increased omnipresent anxiety.
5	Patient reported marked fatigue and dyspnea on exertion, accompanied by “cognitive fatigue” particularly later in the day. Patient says they were so fatigued and short of breath on several doctor’s visits that they couldn’t get up, and the doctors said they would need to be hospitalized if they couldn’t, but they did. Patient had had 1st booster vaccine at the time of infection. Since time of infection, patient feels a little better but still has “mental fatigue”. By the end of the day, they feel “mentally empty”, like they can’t think, and are really “spent”. Sleep is somewhat interrupted and patient is taking Atarax for sleep. Post-COVID concentration deficit. Like many people with these syndromes, patient scores well on these standard cognitive tests but has marked complaints of cognitive fatigue particularly late in the day.	Patient initially reported notable benefit from methylphenidate. It helped with fatigue and concentration and to get work done. However, patient had had a very busy 6-week period which led to the resurgence of fatigue and insomnia; methylphenidate was increased to 10 mg per day. Patient reported difficulty sleeping but thought that insomnia was due to stress. Reported some dyspnea and used an inhaler. Patient continued to report fatigue and dose was further increased to 10 mg twice a day. He reported a distinct improvement in cognitive deficits but only a mild amelioration of fatigue.
6	COVID long-hauler with concentration and working memory problems. Like most persons with these syndromes patient doesn’t have any gross deficits on neuropsychological screening but they are affecting his daily life. He was on Modafinil, which was switched to methylphenidate.	Patient experienced many side effects at first: blurry vision one hour after dose, headaches, cognitively more confused and foggier. However, despite these side effects, patient did report that they had improved energy and less fatigue. most of the side effects went away except minimal headaches. Definitely reported more energy. More confident with tasks. Once again able to do mindfulness exercises/meditation which helps patient concentrate. Patient still had difficulties with language and reading and was seeing a speech therapist. Had no problem with IADLs but fatigue frustrated his ability to complete tasks.

Table 1. Qualitative Visit Notes on Pre-/Post-Psychostimulant Drug

Subject

Pre-drug

Post-drug

Patient described problems with word finding and slow speed of processing. Symptoms better in the morning and get worse in the afternoon as the day goes on. patient is an attorney and writes all day for work. Also has some troubles conversing and preparing for any kind of legal argument. Patient also described troubles with short-term memory and repeating themself. Had to keep lists in personal life, but not so much in his work life. Finds that brain fog comes and goes particularly alongside their physical condition. For example, if they are physically fatigued.

Patient continued to complain of problems with concentration and sustained attention as well as fatigue. Patient did not respond well to Ritalin and went back on modafinil (200 mg). Medication stopped; patient returned to new “normal” baseline.

Patient reported dyspnea on exertion, easy fatigability, and difficulties with memory and concentration. Finds that when having a conversation thy often forget what their partner said. Patient’s partner had noticed this and is the reason they came to the COVID clinic. Subjective memory complaints which impair the patient occupationally, but remarkably patient was quite normal on formal neuropsychologic testing.

Patient had been taking Ritalin currently 5 mg with breakfast and lunch did not notice any benefit nor any side effects at this time. At the beginning patient reported having headaches for a few days but they went away. Patient reported that they do not notice that Ritalin has significantly affected cognition for the better, nor any adverse events. Patient did not notice any benefit nor any significant adverse events from low-dose Ritalin and the dose increase the dose to 10 mg twice daily. Patient developed slight stuttering and poor appetite after the dose increase. However, he did not notice any improvement in his brain fog or concentration and methylphenidate was stopped.

Severe case of COVID-19, had collapsed lung and pneumonia. Patient reported problems with memory, concentration and also possible language. Unable to read or write for a several months following COVID-19 infection. Difficulty writing. Cannot keep track of the day or what they are doing. Sometimes they lose track of whole days or sections of the day. Easily overstimulated and when overstimulated has a hard time concentrating. Sometimes has to pull over and take a rest while driving to calm their mind down. Has to use their GPS or they will get lost even in their own neighborhood. Describes trouble with sustained attention.

Started patient on methylphenidate (Ritalin) 5 mg in the morning with breakfast and as instructed to increase after 2 weeks to 5 mg with breakfast and lunch (10 mg total). They had a lot of adverse effects and stopped the medicine after approximately 10 days. These adverse effects included nausea, some vomiting, and disturbed sleep. They really tried quite hard to stick with the medicine hopefully go away but they did not. Once stopped the medication, the side effect dissipated in a couple of days and they are back to their normal self. They describe some dissociative symptoms and also problems with retrieving information and concentration.

Had mild case of COVID-19 in December 2021. Around March 2022 patient noted that they were not thinking as clearly as they should. Patient describes it “like a heaviness on their brain that slows them down”. Patient described struggling under any “mental or physical exertion”. For example, they feel that the “stress of today’s visit will exhaust them”. Post-COVID complaints of problems with concentration, and some modest deficits on testing (recall and lexical fluency). Patient has had to stop working due to cognitive changes. Patient found they were making mistakes, taking longer to get the same amount of work done, and had to finish up the day at home because they had to double-check everything, they had done at work that day.

Patient reported improved cognitive energy and focus. Patient had a greater ability to complete tasks, used to leave everything pretty much half-done but now not as much. However, patient reported notable ups and downs, the downs he refers to as “crashes”. Some of them seemed related to medication wearing off, i.e., getting cognitively fatigued at around 3 p.m. This was not a consistent symptom. Patient reported no adverse effects: Ritalin hasn’t affected sleep or appetite, or increased omnipresent anxiety.

Patient reported marked fatigue and dyspnea on exertion, accompanied by “cognitive fatigue” particularly later in the day. Patient says they were so fatigued and short of breath on several doctor’s visits that they couldn’t get up, and the doctors said they would need to be hospitalized if they couldn’t, but they did. Patient had had 1st booster vaccine at the time of infection. Since time of infection, patient feels a little better but still has “mental fatigue”. By the end of the day, they feel “mentally empty”, like they can’t think, and are really “spent”. Sleep is somewhat interrupted and patient is taking Atarax for sleep. Post-COVID concentration deficit. Like many people with these syndromes, patient scores well on these standard cognitive tests but has marked complaints of cognitive fatigue particularly late in the day.

Patient initially reported notable benefit from methylphenidate. It helped with fatigue and concentration and to get work done. However, patient had had a very busy 6-week period which led to the resurgence of fatigue and insomnia; methylphenidate was increased to 10 mg per day. Patient reported difficulty sleeping but thought that insomnia was due to stress. Reported some dyspnea and used an inhaler. Patient continued to report fatigue and dose was further increased to 10 mg twice a day. He reported a distinct improvement in cognitive deficits but only a mild amelioration of fatigue.

COVID long-hauler with concentration and working memory problems. Like most persons with these syndromes patient doesn’t have any gross deficits on neuropsychological screening but they are affecting his daily life. He was on Modafinil, which was switched to methylphenidate.

Patient experienced many side effects at first: blurry vision one hour after dose, headaches, cognitively more confused and foggier. However, despite these side effects, patient did report that they had improved energy and less fatigue. most of the side effects went away except minimal headaches. Definitely reported more energy. More confident with tasks. Once again able to do mindfulness exercises/meditation which helps patient concentrate. Patient still had difficulties with language and reading and was seeing a speech therapist. Had no problem with IADLs but fatigue frustrated his ability to complete tasks.

**Table 2.** Demographic Characteristics, Baseline, Follow-Up Scores and Adverse Effects Reported by the Patients
	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6
HVLT: Hopkins verbal learning test; GI: gastrointestinal.
Age	32	36	56	56	40	38
Sex	Male	Male	Female	Male	Female	Male
Race	Caucasian	Caucasian	Caucasian	Caucasian	Caucasian	Caucasian
Weight (pounds)	194	291	203	201	157	160
Duration of long-COVID symptom	1.9 years	2.4 years	2 years	2.2 years	2.7 years	1.9 years
Comorbidities	None	H/O concussion	None	None	None	None
Methylphenidate dose	5 mg	20 mg	5 mg	10 mg	20 mg	10 mg
Follow-up interval	4 weeks	4 weeks	3 weeks	4 weeks	8 weeks	4 weeks
Treatment duration	10 days	16 days	10 days	10 months	3 months	1 year
HVLT immediate recall - baseline	29	32	25	26	34	26
HVLT immediate recall - follow-up	33	35	32	25	36	31
HVLT delayed recall - baseline	9	12	11	8	12	10
HVLT delayed recall - follow-up	12	12	12	9	12	11
HVLT delayed recognition - baseline	11	24	23	19	24	24
HVLT delayed recognition - follow-up	5	4	4	10	12	10
Oral trail A - baseline	21.79	8.1	18.47	9.8	6.34	7.48
Oral trail A - follow-up	13.17	8.6	15.39	9.42	6.35	6.67
Oral trail B - baseline	48	24.87	43.11	32.9	38.82	32.61
Oral trail B - follow-up	55.2	27.93	35.58	26	27.3	34.8
Letter-cued verbal fluency - baseline	17	51	24	26	40	25
Letter-cued verbal fluency - follow-up	21	44	30	24	37	31
Category-cued fluency - baseline	44	61	40	49	67	41
Category-cued fluency - follow-up	40	64	41	55	78	44
Adverse effects reported	Fatigue	None	Disturbed sleep, GI upset	None	None	None

Table 2. Demographic Characteristics, Baseline, Follow-Up Scores and Adverse Effects Reported by the Patients

Patient 1

Patient 2

Patient 3

Patient 4

Patient 5

Patient 6

HVLT: Hopkins verbal learning test; GI: gastrointestinal.

Age

Sex

Male

Female

Male

Female

Male

Race

Caucasian

Weight (pounds)

194

291

203

201

157

160

Duration of long-COVID symptom

1.9 years

2.4 years

2 years

2.2 years

2.7 years

1.9 years

Comorbidities

None

H/O concussion

None

Methylphenidate dose

5 mg

20 mg

5 mg

10 mg

20 mg

10 mg

Follow-up interval

4 weeks

3 weeks

4 weeks

8 weeks

4 weeks

Treatment duration

10 days

16 days

10 days

10 months

3 months

1 year

HVLT immediate recall - baseline

HVLT immediate recall - follow-up

HVLT delayed recall - baseline

HVLT delayed recall - follow-up

HVLT delayed recognition - baseline

HVLT delayed recognition - follow-up

Oral trail A - baseline

21.79

8.1

18.47

9.8

6.34

7.48

Oral trail A - follow-up

13.17

8.6

15.39

9.42

6.35

6.67

Oral trail B - baseline

24.87

43.11

32.9

38.82

32.61

Oral trail B - follow-up

55.2

27.93

35.58

27.3

34.8

Letter-cued verbal fluency - baseline

Letter-cued verbal fluency - follow-up

Category-cued fluency - baseline

Category-cued fluency - follow-up

Adverse effects reported

Fatigue

None

Disturbed sleep, GI upset

None

**Table 3.** Cognitive Assessment Scores at Baseline and Follow-Up Analysis Results
	HVLT immediate recall	HVLT delayed recall	HVLT delayed recognition	Oral trail A	Oral trail B	Letter-cued verbal fluency	Category-cued verbal fluency
HVLT: Hopkins verbal learning test.
Difference in mean (SD)	3.33 (1.02 - 5.64)	1 (0.75 - 1.93)	1.16 (-7.38 - 5.04)	2.06 (-0.84 - 4.9)	2.25 (-3.98 - 8.48)	3.3 (0.89 -7.56)	3.3 (0.89 - 7.56)
z	-2.18	-2.19	-1.12	1.69	0.85	-0.34	-1.53
Hedge’s g	0.91	0.71	-0.21	-0.40	-0.23	-0.64	0.25
P-value	0.006	0.019	0.35	0.93	0.79	0.36	0.05

Table 3. Cognitive Assessment Scores at Baseline and Follow-Up Analysis Results

HVLT immediate recall

HVLT delayed recall

HVLT delayed recognition

Oral trail A

Oral trail B

Letter-cued verbal fluency

Category-cued verbal fluency

HVLT: Hopkins verbal learning test.

Difference in mean (SD)

3.33 (1.02 - 5.64)

1 (0.75 - 1.93)

1.16 (-7.38 - 5.04)

2.06 (-0.84 - 4.9)

2.25 (-3.98 - 8.48)

3.3 (0.89 -7.56)

3.3 (0.89 - 7.56)

-2.18

-2.19

-1.12

1.69

0.85

-0.34

-1.53

Hedge’s g

0.91

0.71

-0.21

-0.40

-0.23

-0.64

0.25

P-value

0.006

0.019

0.35

0.93

0.79

0.36

0.05