PANDAS Clinical Cases

PANDAS clinical cases from our practice

Below are few examples of real clinical cases of PANDAS seen and treated in our offices during the past couple of years.

Here are few important conclusions we have reached while working with approximately 400 PANDAS patients with folow-ups for a year or longer:

(1)	It is likely that a significant number of patients with a sudden onset of tics and/or Obsessive Compulsive Disorder and most of the patient with pre-pubertal onset of Anorexia nervosa (please, see notes below on) but without so-called co-morbid condition may have PANDAS syndrome.

(2)	Incidence of PANDAS appears higher among boys than girls (3:1 ratio).

(3)	Patients are likely to belong to a certain phenotype (described below!).

(4)	Patient's initial symptoms may manifest itself as early as 15 - 18 months of age and may be easily misunderstood or completely missed.

(5)	If the first clinically recognized episode occurs after the age of 8 (and especially after the age of 10), it is unlikely true initial episode, but the recurrent one. Previous episodes were likely not recognized as such.

(6)	One of frequently missed symptoms is a significant deterioration in fine motor skills (writing and drawing) and regression in math skills.

(7)	.A severe and debilitating separation anxiety appears regularly in almost every case and does not wane down significantly even during the remission of other symptoms.

(8)	In patients who may present with anorexia nervosa as a symptom of PANDAS, there is a distinct anamnestic information usually obtainable from the patient. While a "classic" anorexia patients most frequently report a "distorted" image of her/his own body, in PANDAS patients with anorexia, the main complaint appears to be a pervasive fear of chocking on food while eating. It is however possible that this initial fear of chocking is later replaced by image distortion.

(9)	During the symptom exacerbation child is likely to have enlarged pupils making him/her to appear terror stricken

(10)	There have been no scientific (or other) evidences presented to date that would justify use of SSRIs in patients with PANDAS. In certain cases an improvement was noted following 2 - 4 weeks of therapy but it is unclear if this improvement was a result of these medications or simply (and more likely) natural waning of symptoms.
	Note of caution: we have seen several patients with PANDAS who had a dramatic negative response to Haldol (haloperidol) and/or Ativan. Within 48 hours of introduction of Haldol patients developed a severedystonic reaction. Ativan was followed by overwhelming panic attacks rendering patients completely dysfunctional. Thiese disturbance persisted throughout the treatment and disappeared spontaneously only upon discontinuation of the drug.

(11)	In our experience PITAND syndrome is unlikely a separate clinical entity, but a classic PANDAS syndrome with a negative group A beta hemolytic Streptococcus titers for whatever reason.

(12)	IVIG appears to be the treatment of choice for PANDAS. In properly diagnosed cases IVIG treatment can be expected to result in a complete and lasting cure of the condition in a significant number of cases. In our opinion other options mentioned in literature (i.e. plasma exchange, plasmapheresis) have much higher complication rate and essentially the same or even lesser benefits.

(13)	Success of IVIG in PANDAS appears to be age-limited. Sometimes during and particularly after the completion of puberty the IVIG treatment is likely to become less effective. This particular statement may have to be corrected in the near future since we have treated successfully several patients after puberty (the oldest patient was 24 years of age).

(14)	Another interesting observation: the actual speed of patient's recovery following an IVIG treatment is likely not dependent on the duration of the illness prior to the treatment. "Conversion" occurs equally quickly in patients who have had symptoms for years and patients who've had them only for few months. It appears however, that in patients younger than 10, noticable improvement in symptoms can occur in matter of *days, while in patients older than 10, this process may take several weeks*.

(15)	Value of long-term antibiotic treatment has not been proven in PANDAS, and our experiences to date do not support its use. Preventative antibiotic following the immunomodulating treatment (IVIG, plasmapheresis, plasma exchange) however is considered a standard.

(16)	Removal of adenoids and tonsills has not shown long-term benefits in treatment of PANDAS.

Updated PANDAS signs and symptoms

(1) Pediatric onset. It is now believed that the first symptoms of PANDAS occur between 18 months and 8 years of age. If the first clinically recognized episode is detected after the age of 8 (and especially after the age of 10), it is unlikely true initial episode, but the recurrent one. Previous episode(s) were simply not recognized as such.

(2) Particular patient phenotype. PANDAS patients are frequently highly intelligent, very communicative child who is also a very good student. It is common that patient's past medical history contains information about occasional ("transient") tic(s), certain degree of obsession with order, cleanness, preciseness, etc.

(3) Presence and/or history of certain psychiatric symptoms.

OCD symptoms (intrusive thoughts, anxiety, different phobias, unfounded fears) are present in virtually ALL cases.

Sleep Disorder(s) (insomnia, inability to fall asleep, fright full sleep, nightmares) in some form is oresent in 84% of patients.

Behavioral regression (separation anxiety, insistence to remain at or close to home, "baby-talk", temper tantrums) in some form has been indentified in 98% of patients.

Aggressiveness (present in 62% of patients).

Hyperactivity and inattentiveness (present 71% of patients).

Learning disability particularly affecting mathematics' skills (present in 62% of patients).

Inability to concentrate (present in 87% of patients). Hallucinations (9% of patients).

Eating disorders (17% of patients) are other frequently present psychiatric symptoms of PANDAS.

(4) Presence and/or history of certain characteristic physical signs and symptoms.

Adventitious movements have been identified in 31% of patients.

Wide pupils (patient appears "terror stricken"; present 83% of patients).

Various and evolving tics (present in 72% of patients).

Deterioration in fine motor skills and handwriting (89% of patients).

Short-memory loss (62% of patients).

Enuresis and/or urinary frequency (88% of patients).

Increased sensory responses (increased sensitivity to light, and/or sound, and/or touch, and/or smell) reported in 39% of all patients.

(5) Characteristic clinical presentation.

- Sudden (sometimes overnight) onset of symptoms. Parents frequently recall the exact date and/or time of the day when symptoms appeared.

- Wax-and-wane pattern of symptoms. Symptoms exacerbation is frequently associated with or may occur following an infectious event and/or live virus vaccine administration

- The initial episode is (usually) associated with GABHS infection, however subsequent episodes do not necessarily have to be related to GABHS.

(6) Significant elevation of GABS antibody titers (i.e., ASO titer, AntiDNase B titer) is common, but not necessarily present in every case. Negative GABS titers do not absolutely exclude the diagnosis of PANDAS.

(7) Measurable clinical improvement following the "Steroid Burst".

Case #1

An 8 year old Caucasian girl from Upstate New York was brought to our offices for a consultation on August 3, 2006. Following a documented Group A Beta Hemolytic Streptococcus infection on February 6, 2005 she had a sudden onset of obsessive-compulsive symptoms (leaf picking, repeating phrases, constantly seeking reassurance, hoarding of trash, picking food wrappers and paper scraps from the garbage, unusual bathroom rituals, such as turning lights on and off, clicking toilet seat 5 times) and vocal tics (grunting, constant throat clearing). There were also severe and debilitating behavioral changes (emotional lability, moodiness, irritability, and extreme separation anxiety). In addition, her fine motor skills (particularly handwriting and drawing) deteriorated noticeably as well as her math skills and ability to concentrate.

During the ensuing 15 months her clinical course exhibited clear "wax-and-wane" pattern, where her OCD symptoms would decrease over a period of time only to be re-ignited by even minor infectious episodes (usually a viral upper respiratory tract infection). The quality and the intensity of her OCD symptoms would change in time. Episodes of running in circles 150 times a day, with a stiff "routine" of 10 runs clockwise and 10 runs counterclockwise would be later substituted by sudden fear of contamination of her parents and grandparents with urine or germs, insistence on symmetry, obsessions with death and/or natural disasters, etc. However, her debilitating separation anxiety and diminished fine motor skills would not improve significantly even during the periods of diminished OCD symptoms.

Her treatment included several courses of antibiotics (usually there was an immediate, but incomplete remission of her OCD symptoms), tonsillectomy (in April 2005), and several attempts to control her symptoms with SSRI. All of these treatments had only temporary effect and by spring/summer of 2006 she became completely incapacitated, home bound, and unable to attend school.

Following a telephone discussion with patient's mother the following laboratory data were obtained: ASO titer (reported as normal!?) and AntiDNase B titer (reported normal as well!?). A "steroid burst" was administered prior to the appointment and the response was considered significantly positive.

Following the office consultation and confirmation of clinical diagnosis of PANDAS on August 4 & 5, 2006 patient received IVIG infusion with an immediate improvement in her core symptoms, particularly her behavioral aberrations. She was discharged home with her parents following the second day infusion and has been kept on a preventative antibiotic. One month follow up report indicated that patient had recovered all of her previously lost and/or diminished functions and that she was free of all of her symptoms, able to attend regular school classes. Three and six months follow up reports confirmed that patient had continued to remain symptom free.

Patient's drawings of a doll BEFORE and immediately AFTER the IVIG treatment
June 2006	September 2006

Case #2

Nine year old Caucasian male from Chicago's suburbs was seen in our offices for consultation on October 03, 2005. One week before the visit patient came home from school with fever and not feeling well. He barely ate and went straight to bed. He woke up at 1 AM complaining of having "bad thoughts" and was not able to fall asleep again. During the next 48 hours his symptoms progressed rapidly. He exhibited fully blown coprolalia (continuous use of "light" obscenities, in his case use of words like penis or vagina within and out of the contest of discussion), tics, severe debilitating separation anxiety, unspecified fears etc. Parents in panic took him to a suburban emergency room where an ER physician obtained a throat culture (positive for Beta Hemolytic Streptococcus Group A) and diagnosed him with PANDAS. Patient was started on amoxicillin-clavunate (Augmentin) and over the next several days his symptoms (particularly coprolalia) gradually abated. However, his behavioral changes (severe separation anxiety, hyperactivity, and withdrawal from others) persisted almost unchanged and he was not able to return to school. Laboratory work-up ordered at the time of visit uncovered borderline ASO titer (200 IU/ml) and significantly elevated AntiDNAse B titer (1,360). Patient was continued on Augmentin and "steroid burst" was administered the following week reportedly diminishing patient's symptoms greatly. Over the period of next 3-4 months patient remained on preventative antibiotic, his symptoms for the most part were kept under control and he was able to return to school. Unfortunately his performance in school was lagging severely, he continued to be withdrawn and suffer from separation anxiety and his parents requested IVIG treatment even with minimized clinical signs of OCD and tics.

IVIG infusion was given in February 2006 and the procedure was tolerated well. At his follow up at one-month post-IVIG parents reported a complete disappearance of ALL of his symptoms (OCD, tics, and behavioral changes). His schoolwork improved almost immediately and his teacher felt that he was back no his normal potential in school as well.

One-year follow up only confirmed patient's complete recovery and no further follow-ups had been scheduled.

Case #3

5 ½ years girl living in Israel following a documented Beta Hemolytic Streptococcus Group A infection in February 2005, developed multiple tics (eyes rolling, head "bobbing", contracting abdominal muscles) and coprolalia (use of "light" obscenities when speaking to parents but NOT to others). She also exhibited significant change in her personality with excessive moodiness, unprovoked crying episodes and severe separation anxiety. Patient was given a 10-days course of oral Penicillin with no improvement in symptoms. Oral steroids were instituted following the antibiotic treatment and an immediate and significant improvement was noticed. At that time she was started on Augmentin with a decent control of her tics but behavioral changes had persisted. In April 2005 following a mild sore throat there was a fully blown recurrence of her symptoms. Again steroids were given and again an immediate improvement was reported. Finally in June 2005 following another worsening of her condition, parents with our assistance made an application to the Ministry of Health of the State of Israel for IVIG treatment that was approved. IVIG infusion was accomplished using our protocol and no significant side effects were reported.

Follow ups of patient's condition at 1 month, and 1 year following the treatment confirmed a complete disappearance of her symptoms and a full recovery.

Case #4

Nine-year old boy from Louisiana presented with an interesting history that may in some ways bring into question certain assertions about the accepted definition of PANDAS age distribution.

At age of 18 months he had a documented Group A Beta-Hemolytic Streptococcus infection that was, within few days, followed by severe and unmistakable OCD symptoms: washing his hands hundreds of times a day and lining things up and becoming extremely upset if the order was disturbed. Since he was not able to communicate his desires (or urges) to his mother appropriately (because of his age and state of his speech development) he would drag her by her finger to the sink and cry "wa, wa" until she would pick him up and let him wash his hands. In addition, he developed severe anxiety over just about everything (eating, foods, shoes, etc.). This bizarre behavior persisted for a while (attending physicians could not explain it adequately). His symptoms slowly waned down but his behavior (anxiety, separation anxiety) persisted and was considered to be a result of family's sudden move overseas. At age of 3 patient had another (documented) Streptococcus infection and there was another resurgence of his bizarre symptoms. Only this time there were multiple motor and vocal tics present as well. Being in a foreign country mother took upon herself to manage this particular episode by obtaining oral steroids. Within a week all patient's symptoms disappeared and he was (at least by her recollection) back to near normal.

Another episode took place at age of 5 when, following another infectious episode patient suddenly developed multiple motor and vocal tics, severe OCD symptoms (changing clothes up 20 times per day, lining puzzles day and night, demanding that parents read and do flash cards at all hours of day and night) and debilitating behavioral changes (severe separation anxiety, moodiness, temper tantrums, etc.). At that time patient was worked up in Louisiana and placed on Zoloft and steroids. Within a week his symptoms abated and he was back to school. At that time his separation anxiety was greatly improved as well and disappearance of symptoms was credited to Zoloft.

In November 2004 patient became ill with high fever, swollen glands and sore throat. Four days later when the symptoms of his illness started to improve he developed extreme anxiety, OCD symptoms and mild tics. By the end of December his behavior became uncontrollable. His separation anxiety was so extreme that he attempted to jump out of the moving car on the way to school. Patient was admitted to a mental hospital for several weeks and was treated with numerous medications but improved only slightly and upon the discharge was not able to return to school.

In January 2005 patient's mother contacted our offices via e-mail and following several communication exchanges decided to bring him for further evaluation and possible treatment.

In June 2005 patient received IVIG treatment and tolerated it relatively well. There were mild side effects at and immediately following the infusion (headaches, several episodes of vomiting and fever), but everything normalized with couple of days.

Follow up by e-mail at 1 and 6 months after the infusion confirmed that he continued to be asymptomatic. There was an episode of recurrence of symptoms approximately 9 months after the treatment (mother reportedly had a Strept infection) and it was easily controlled with 5 days of Prednisone.

How and when should you suspect that your child has PANDAS

PANDAS diagnosis has been present in medical literature for over a decade but it is still, for some reason, controversial. Consequently, most of medical professionals in the US and throughout the world are not familiar with this condition. Even those few who are, do not know what are the treatment options and if they do, they remain are hesitant to use them. Below are few pointers for parents who may suspect that their child has PANDAS.

Pointers to diagnosis of PANDAS:

(1) A sudden and a significant change in your child's behavior that follows an infection within days (or possibly few weeks) for which no other rational explanation can be found. Changes occur in three different areas of behavior and they can present itself one at the time, some at the time or all of them together.

	Obsessive-compulsive symptoms can vary greatly. Obsession with mechanical devices (i.e. fans), running in circles in a predictable manner, hoarding of trash or other useless objects, death thoughts, unusual fears (fear of natural disasters, fear of not being able to fall asleep, etc.), repetition of obscene words or phrases, repetition of certain physical (hand washing, clothing change, clicking lights certain number of times, etc.) or mental activities (incessant praying or repeating certain words or mantra), insistence on certain order of things, hair plucking, unfounded fears of enclosed spaces (agoraphobia), germs, being contaminated by body fluids (urine, saliva) are some of the common symptoms. Use of obscenities (within or out of the contest of discussion) is a common symptom. When asked why, children usually state that "something" is making them say these words.
	Physical symptoms of PANDAS frequently include tics and a significant deterioration in fine motor skills. Tics can be isolated or may come in multiples and in bursts. They can be especially noticeable when child is tired, irritated, or left alone. Common tics include eye blinking, tapping, facial grimacing (motor tics), or coughing, throat clearing, uttering words for no apparent reason (vocal tics). Less frequently child can have unexplainable purposeless motions with all four extremities that look like a weird dance (St. Vitus dance was an early description of this symptom). Interestingly enough, despite of obvious shaking of hands child is able to use fork and spoon without spilling food. One of the hallmark symptoms is an obvious deterioration in writing and drawing skills. Urinary frequency and/or bed wetting have been reported frequently. Wide pupils (especially during the symptoms' peaks), and increased sensory sensitivity (to light, sound, smell, and/or touch) are also common.
	The unheralded common symptom in most children with PANDAS is a severe and debilitating separation anxiety. Previously outgoing, socially well adapted and extremely communicative child becomes parent-bound, and refuses to go to school, attend even previously favored activities or to go to bed alone. Sooner or later their behavior forces them to drop out of school (temporarily or for longer periods of time). And even when they return, combination of unfounded fears, unexplainable anxiety and diminished physical (see above deterioration in fine motor skills) and academic (significant decrease in math skills, reading and writing difficulties) capabilities only increases their frustration further.

(2) Symptoms eventually (with or without the treatment over a period of weeks or months) slowly wane down until becoming almost unnoticeable. Since this frequently coincides with the institution of phychopharmaceuticals to control child's symptoms, these drugs are incorrectly credited with the symptoms improvement. Behavioral changes, particularly separation anxiety however, are less likely to abate completely and to a certain degree persist even during the period when other symptoms are absent.

(3) Frequently, there is a history of Group A Beta-Hemolytic Streptococcus infection (sore throat with swollen glands and fever, or a sinus infection, i.e.), and in recurrences, Strept infection in the patient or patient's household members. We have seen few patients in whom the history of Streptococcus infection could not be elicited but in at least two of them an elevated Mycoplasma Pneumonia titers were reported.

(4) During symptomatic periods patient appears distant (like "he/she is not there" or instead of looking "at you" is looking "trough you") and frequently has visibly dilated (large) pupils.

(5) PANDAS is more likely to occur in certain "phenotype" of children:

	In children with a history of an early speech development, and who (usually) (prior to the illness) excel in school, particularly in math and sciences.
	In children who normally exhibit certain amount of obsessions with order, punctuality, preciseness, school work, etc., before the illness.
	Parents of children with PANDAS are more likely to be either highly educated or extremely enterprising. Even more likely is that the mother of a child with PANDAS is highly intelligent, has a history of being good in math and with computers (computer-savvy), and can exhibit certain degree of obsession with punctuallity and order.

Possible Adolescent-Adult Variation of PANDAS is under review!

We have indentified a small group of patients with what appears to be an adolescent-adult "variant" of PANDAS. Hallmark symptoms in these patients include an unrelenting, debilitating anxiety, chronic fatigue, and an eating disorder. All patients in this group have exhibited a chronic non-specific gastrointestinal symptoms and have elevated AntiDnase B titer.

Symptoms usually start in high school (freshman or sophomore year).

Initial symptom (present at one time in almost every patient): chronic, not fully explained and/or diagnosed GI ("stomach") complaint (common diagnosis attached to the complaint: GE reflux). Non-specific epigastric or abdominal pains, "heart burn", "fullness" following a meal, occasional morning nausea and/or vomiting are common. Few patients report loose stools but no clinical picture of diarrhea has been elicited. GI symptoms may disappear at the onset of psychiatric symptoms, or they may continue but with decreased intensity or remain unchanged.

Insidious development of an overwhelming anxiety. Anxiety usually developes over relatively short period of time (matters of days or weeks). Patients report waking up in the morning with a feeling of an overwhelming (unexplainable) anxiety that may persist throughout the day and can wane slowly towards the evening. An appropriate literary description of these symptoms can be found in Goethe's "Sorrows of (young) Werter". There has been no discernable connection established between a documented (or distinctly recalled) infectious event and the actual onset of anxiety episodes. There is no "wax-and-wane" pattern of symptoms, however patients appear to be much more comfortable (and thus feels better) in socially non-challenging situations and at home. There is a tendency toward avoidance of going out (of the house), avoiding friends and skipping previously favored activities. Patients are unable to establish appropriate peer and/or boyfriend-girlfriend relationships. Eventually they may stop going to school (or to classes, if college students), curtail or seize completely their social activities and become home bound.

Intrusive thoughts are present in most patients.

Severe and persistent sleep disturbances.

Behavioral regression(s).

Insecurity and separation anxiety (adolescent type).

Chronic fatigue commonly present.

Following several years of symptoms, presence of clinical depression is common!

If your child has been exhibiting some or most of the symptoms described above, you must bring the possibility of PANDAS diagnosis to your doctor's attention. Be aware that this diagnosis has yet to be universally accepted within the medical community, and your doctor may not know about it or believe that it exists. If you feel that our office can be of any assistance to you, do not hesitate to send us an e-mail with detailed description of your child's symptoms. We would be glad to review it and reply ASAP. We will reply only to e-mails sent by parents or legal guardians of children suspected of having PANDAS. E-mail must contain full name and address of the sender and child's age.

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