A cross-sectional observational sociological study was conducted in Italy between December 2023 and May 2024, involving specialist neurologists, pediatric neuropsychiatrists with expertise in DEEs (LGS and DS), and caregivers of patients affected by DEEs/LGS and DS.

The survey was carried out using standardized questionnaire-based interviews. Specifically, two questionnaires were used: one administered to a sample of 47 physicians (37 neurologists/neuropsychiatrists for DEEs/LGS and 10 specializing in DS), distributed by geographical area, and another to 30 caregivers, also geographically distributed and exclusively of DEEs/LGS patients, also geographically distributed. Caregivers included both those of patients with DEEs/LGS (n = 12) and those of patients with Dravet Syndrome (DS; n = 18). The complete questionnaires used in this study are available as supplementary materials.

Participants were recruited randomly through internal databases from Bhave, with a small proportion (less than 5% of respondents) recruited through reference clinicians using snowball sampling.

For physicians:

Specialization in neurology, pediatric neuropsychiatry, or neuropediatrics (hospital pediatrician)

The project was structured into two main phases with the following specific objectives for each phase:

Quantitative Research—Organizational Models (Physicians and Healthcare Facilities): This first phase aimed to identify, define, and quantify the main organizational models for the management of DEEs patients, particularly those with LGS. This phase sought to compare emerging healthcare and social care organizational models with those related to other rare DEEs, such as DS.

The entire research process was conducted in compliance with the ethical guidelines and codes of conduct of EphMRA (European Pharmaceutical Market Research Association), ASSIRM (Italian Market Research Association), ICC, ESOMAR, and Farmindustria. Questionnaires were administered in compliance with Italian privacy laws, pharmacovigilance regulations, and the Italian Communications Authority (AGCOM). Data were processed anonymously and confidentially to ensure privacy protection and compliance with personal data protection regulations (EU Regulation 2016/679—GDPR). The study was also conducted in accordance with the principles of the Declaration of Helsinki.

The questionnaires were specifically developed and validated by a multidisciplinary board of research methodologists, neurologists, and neuropsychiatrists. The design followed key methodological criteria: -

Intersubjectivity: ensuring evaluations were independent of the interviewer's subjective judgment.

The study aimed to reconstruct the Patient Journey of individuals with DEEs/LGS and DS. This model integrated sociological and anthropological perspectives, examining care processes at three levels:

Micro-level: individual experiences and illness narratives (16, 17), focusing on how patients and caregivers assign meaning to symptoms, diagnosis, treatments, and interactions with professionals.

All quantitative data were analyzed using IBM SPSS Statistics v.29 (IBM Corp., Armonk, NY, USA). Descriptive statistics (frequencies and percentages) were reported for categorical variables, while means and standard deviations were calculated for continuous variables. Differences between groups (e.g., LGS vs. DS, physicians vs. caregivers) were tested using Chi-square (χ²) tests or Fisher's exact test for categorical variables, and independent-samples t-tests for continuous variables. When comparing more than two groups, ANOVA was used, followed by Bonferroni post-hoc tests. A significance level of p < 0.05 was considered statistically significant. For proportions, 95% confidence intervals (CIs) were calculated. To estimate the magnitude of differences, effect sizes were reported (Cohen's d for means, Cramer's V for proportions).

Data were collected through standardized Computer-Assisted Web Interviewing (CAWI), Computer-Assisted Telephone Interviewing (CATI), and Face-to-Face (F2F) methods. The average interview duration was approximately 20 min for physicians and 25 min for caregivers. Questionnaires were developed by a multidisciplinary board of methodologists, neurologists, and neuropsychiatrists, and were organized into four main sections: (A) respondent profile, (B) organizational models and procedures, (C) patient journey reconstruction, and (D) transition to adulthood.

A total of 77 respondents participated in the study: 47 physicians and 30 caregivers. Among the caregivers, 18 were relatives of individuals with DS and 12 were relatives of individuals with DEEs/LGS. This distribution was considered in all subsequent analyses, and percentages are reported together with absolute numbers (n/N) to ensure transparency. When interpreting differences between DS and DEEs/LGS caregivers, results should be read with caution given the smaller sample sizes of the subgroups.

The caregiver sample consists primarily of parents of patients; however, siblings of affected patients also represent a portion (12% of the sample). To ensure comprehensive analysis, caregivers of patients of different ages were included, providing a complete picture of the journey and focusing on a particularly critical phase: the transition from pediatric to adult care. The most represented caregiver group corresponds to patients aged 18–29, with a significant portion also caring for minors (24%) and patients over 30 (12%).

The majority of caregivers interviewed are homemakers or part-time employees, with 83% reporting that their current employment status is influenced by their role as a caregiver for a patient with a rare disease. To facilitate interpretation, results were structured to distinguish between physicians' and caregivers' responses, with explicit comparisons across syndromes (DS vs. DEEs/LGS) and between respondent groups where relevant.

Among the responding physicians, 78% are specialists in Neurology, 19% in Pediatric Neuropsychiatry, and only 3% in Pediatrics. A key distinction emerges based on the specific area of expertise: 76% of those treating DEEs/LGS are neurologists, whereas an overwhelming majority of specialists managing DS patients are pediatric neuropsychiatrists (83% of the sample), as this reflects the age at which the diagnosis is definitively made.

Looking more closely at the characteristics of the healthcare facilities where the surveyed physicians practice, distribution across Italy is uneven, with most facilities concentrated in Northern and Central Italy. In addition to hospitals, which account for 24% of participating institutions, the largest proportion of respondents are from university-affiliated healthcare centers (43%).

This section first reports physicians' responses regarding team composition and organizational practices, followed by caregivers' perspectives on the availability of support services. Comparative analyses are presented both between syndromes (DS vs. DEEs/LGS) and between respondent groups (physicians vs. caregivers).

The distribution of patients among the centers surveyed showed a significant percentage of patients coming from outside their region of residence: 24% for pure LGS, 27% for LGS-like cases, and 16% for other DEEs. In the case of pure and LGS-like cases, most patients came from central and southern regions, particularly Calabria, Campania, Abruzzo, and Puglia. However, the regional distribution shifts when looking at out-of-region patients with other DEEs, who are reported by specialists to mainly come from Basilicata, Molise, and Calabria.

Despite the complexity of these conditions and the urgent need for an integrated multidisciplinary approach, patient management remains predominantly entrusted to a single specialist (65% of cases), with occasional involvement of other professionals such as physiatrists, hospital pediatricians, and psychologists, the latter almost always external to the facility. The main obstacles to the creation of multidisciplinary teams are reported to be organizational and logistical challenges, as well as the absence of certain specialists within the facility or the lack of initiative to propose their creation (Figure 1).

Where available, the team consists primarily of a neurologist—who, in most cases, is responsible for therapeutic decisions—a pediatric neuropsychiatrist, a physiatrist, a psychologist, and a neurosurgeon, with the latter almost always being an in-house specialist. A significant proportion of teams (27%) do not hold multidisciplinary meetings, while those that do have a mean interval of 22 days between meetings, which are predominantly conducted in person and, in some cases, online. From a social dimension, the absence of regular multidisciplinary meetings in more than one-fourth of DEEs/LGS centers reveals a structural gap in coordination, with potential consequences on patients' and families' social support networks. However, this difference compared to DS teams (18%) did not reach statistical significance [χ²(1) = 0.96, p = 0.33].

Regarding the services available at the centers for patients and their families, the findings highlight the presence of psychological support services for patients and, in some cases, for their families. In addition to psychological support for patients who cannot easily travel to the center or are cared for at home, 69% of facilities provide training programs on disease management and therapies, while 22% offer remote monitoring systems. However, patient support programs offered by private companies are completely absent.

From a psychological dimension, these findings highlight the limited integration of emotional support services for DEEs/LGS families, despite the high burden of care. The stronger presence of training initiatives in these centers reflects a partial but important response to caregivers' need for empowerment.

Psychological support services were more frequently available for DS families (12/18; 66%) than for DEEs/LGS families (5/12; 43%), a difference that reached statistical significance [χ²(1) = 4.02, p = 0.045; 95% CI difference: 1.2%–44.1%]. Conversely, caregiver training programs were significantly more frequent in DEEs/LGS centers (8/12; 69%) than in DS centers (3/18; 17%) [χ²(1) = 18.21, p < 0.001; Cramer's V = 0.41, large effect size].

In this section, results are presented separately for physicians and caregivers, and comparisons between DS and DEEs/LGS are reported where applicable.

Regarding the transition to adult care centers, caregivers of DEEs/LGS patients report that this process begins at age 18 in 29% of cases. The remaining respondents describe highly variable situations, reflecting the lack of structured procedures: in 14% of cases, the transition occurs after the patient turns 20 or 25; in 7%, it occurs only when necessary; and in another 14%, the process is left entirely to the family, which has to find a suitable center on its own. A significant proportion of respondents do not know when the transition will occur, partly due to a lack of information, but also because they are caregivers of patients who have not yet reached the transition age. Among families currently being cared for by a pediatric center, 75% report that the topic is not discussed, primarily because the caregivers themselves prefer that their loved ones continue to receive care from the same facility.

Among those who have transitioned, a concerning 57% of caregivers state that the entire process was their responsibility, as the pediatric reference center did not have a structured transition pathway, leaving families to find an adult center on their own (Figure 2).

When a pathway exists (reported in 28% of cases), it mainly involves joint consultations between pediatric and adult neurologists, followed by the transfer of medical records and patient referrals to the new center. In other cases, the transition simply consists of the pediatric center scheduling an appointment with the new specialist. The entire transition process takes a mean of 12 months, and in 30% of cases, caregivers report that it was not formally organized by the reference center. Additionally, the involvement of general practitioners in the transition process is generally not foreseen.

In adulthood, many treatments essential for rehabilitation and quality of life are discontinued: half of the caregivers surveyed report that their loved one is no longer receiving treatment or therapy, while smaller proportions continue to receive support from behavioral educators, nutritionists, physiatrists, cardiologists, or physical therapists.

Looking at the transition process, a particularly alarming finding concerns the emotional state most commonly reported by caregivers: fear, specifically related to concerns about inadequate care and dealing with their loved one's cognitive delays. Overall, caregivers perceive a decline in the quality of care when transitioning from pediatric to adult care, with the most critical issues in the patient journey being seizure management and daily condition management, exacerbated by a severe lack of communication and support. From an administrative-bureaucratic dimension, the transition often coincided with discontinuities in exemption renewals and care plans, representing a critical barrier to continuity of care.The difference in dropout rates between LGS patients (5/12; 40%) and DS patients (7/18; 38%) was not statistically significant [χ²(1) = 0.12, p = 0.73; 95% CI for difference: −12.5% to +16.3%].

To address these concerns, caregivers believe that the most urgent actions should focus on providing greater material and psychological support to families, as well as raising awareness among health care providers about the importance of listening to and respecting caregivers and patients.

This section focuses on direct comparisons between DS and DEEs/LGS caregivers, while physicians' responses are reported only when relevant differences between syndromes were observed.

A comparative analysis of management models in the therapeutic areas of DEEs/LGS and DS revealed notable differences in how centers operate.

Regarding the transition to adulthood, the DS model appears to be more structured, with only 17% of DS centers lacking a formal transition pathway compared to 54% in the DEEs/LGS area. However, previous studies (7) have shown that many so-called structured pathways exist primarily on paper and fail to meet the actual care needs of patients and families during this critical phase. Moreover, transition pathways, where available, have existed in both areas for approximately 10 years, and in the DS model, they involve greater participation from general practitioners.

In terms of patient care and support services, DS patients have better access to management tools: 83% of DS centers offer remote telemonitoring for patients who cannot easily visit the center, and 66% provide psychological support services (compared to 43% for DEEs/LGS). However, the situation is reversed when it comes to training programs for condition and therapy management: only 17% of DS centers offer such training, compared to 69% of DEEs/LGS centers.

In terms of therapeutic choices, physicians report that the hospital drug formulary imposes greater restrictions on DS patients than on those with LGS and other DEEs. On a scale from 1 to 7, agreement with the statement “At my center, the hospital drug formulary imposes limitations on therapeutic choices for LGS patients” scores 3.15 for DEEs vs. 3.58 for DS. Probably, this is not only due to the formulary but also to the contraindications of a large group of drugs (sodium channel blockers) in Dravet syndrome due to its genetic defect. Cost factors, however, seem to pose a smaller barrier for DS patients, with agreement on the statement “At my center, the cost of drugs limits therapeutic choices for LGS” rated 3.23 for DEEs/LGS and 2.83 for DS. Although the mean values indicate a trend toward greater formulary restrictions for DS patients (mean 3.58) compared to DEEs/LGS (mean 3.15), this difference did not reach statistical significance [t(45) = 0.74, p = 0.46]. Similarly, the difference in perceived cost-related limitations (DEEs/LGS: 3.23 ± 1.4 vs. DS: 2.83 ± 1.3) was not statistically significant [t(45) = 1.02, p = 0.31]. Nevertheless, despite the absence of statistical significance, these directional trends remain noteworthy from an interpretative and organizational perspective. The slightly higher formulary restriction scores reported by physicians managing DS patients may reflect the presence of more institutionalized and protocol-driven care pathways, which, while ensuring treatment standardization, can also limit individual clinical discretion in therapeutic choices. Conversely, cost-related constraints appear somewhat less influential in DS management, possibly due to the consolidation of dedicated care networks and funding mechanisms that support long-term management. Although these findings should be interpreted descriptively, they reveal structural and behavioral dynamics that warrant further investigation beyond purely statistical significance.

Regarding the transition age, the delayed shift to adult care in DS patients is confirmed (Figure 3). This difference can also be interpreted through a political-institutional dimension, as DS benefits from stronger advocacy, institutional recognition, and dedicated policies, which may partly explain the more structured but delayed transition models.

The proportion of patients transitioning after 25 years was significantly higher among DS patients (4/18; 22%) compared to DEEs/LGS patients (1/12; 6%) [χ²(1) = 6.85, p = 0.009; Cramer's V = 0.28], suggesting a moderate association between syndrome type and delayed transition.

While 54% of DS patients (10/18) transitioned at 18 years of age, a significant proportion (4/18; 22%) transitioned after 25 years, compared to only 5%–6% in DEEs/LGS. Additionally, 12% of (2/18) DS cases had no documented transition at all.

Finally, the cultural dimension emerged in the way families interpreted and negotiated illness trajectories: while DS was more frequently framed within a recognized and institutionalized condition, DEEs/LGS remained less visible, with families often perceiving marginalization and lower societal awareness.

In terms of perceived attitude of families toward transition to adult care centers, DS families appear to be significantly more accepting of the process (60% of cases vs. 14% of DEEs/LGS patients). For both groups, initial resistance is primarily due to fear of losing their trusted specialist. However, for LGS and DEEs patients, this concern is compounded by the lack of an integrated transition pathway to adult care. In the case of DEEs/LGS, 14% of patients strongly resist the transition, and 11% do not accept it, while the majority of families are initially hesitant (61%).

The dropout rate from adult care centers is similar across conditions, with clinicians estimating that approximately 40% of patients discontinue care within the first 18 months of transition. After this period, patient management is primarily home-based, often under the supervision of a private specialist.

Regarding the main challenges encountered in patient care, physicians report that diagnostic difficulties are a major issue for both DEEs/LGS and DS. However, from the families' perspective, physicians identify seizure control as the primary difficulty for DEEs/LGS patients, who continue to experience frequent seizures into adulthood, whereas communication and psycho-cognitive issues pose greater challenges for DS patients.

The study also aimed to reconstruct key stages of the patient journey for Dravet Syndrome (DS), as reported by pediatric neuropsychiatrists and adult neurologists, to compare it with findings from previous research (9) and with the care pathway for DEEs/LGS patients. For the latter, a unified journey was mapped, highlighting specific differences in the case of LGS patients.

Clinicians report an mean diagnostic timeframe of 4 months from the onset of first symptoms (8 months for DEEs and 7 months for LGS according to neurologists, and 13 months for DEEs and 16 months for LGS according to pediatric neuropsychiatrists). However, they rarely indicate that this timeframe exceeds 12 months, contrasting with caregiver reports and previous case studies, which suggest significant diagnostic delays spanning several years. In the case of DEEs and LGS, a larger proportion of clinicians acknowledge diagnostic delays beyond 12 months: 19% of DEEs patients and 24% of LGS patients according to neurologists, and 29% of DEEs patients and 22% of LGS patients according to pediatric neuropsychiatrists.

For DS, diagnostic delays are reported as occasional in 67% of cases, compared to 73% for DEEs/LGS according to neurologists and 56% according to pediatric neuropsychiatrists. The consequences of these delays include a negative impact on development and seizure control, non-specific or only partially effective therapeutic choices, and delays in receiving genetic test results. These findings align with the different onset patterns of the two syndromes: DS symptoms appear early and present distinct clinical features, whereas LGS takes longer to fully manifest, delaying the confirmation of diagnostic criteria.

The most commonly performed diagnostic tests include sleep and awake EEG (for almost all DEEs and LGS patients), awake EEG, MRI scans. Also, genetic testing is often performed. These procedures primarily involve pediatric neuropsychiatrists, neurologists, psychologists, and primary care pediatricians (Table 1 and 2). The diagnosis is made by the pediatric neuropsychiatrist, but a psychologist is present in only 25% of cases.

Routine follow-up visits occur at a mean interval of 4 months for DS patients and are conducted almost exclusively in person at the healthcare facility. Remote consultations are rare, with 7% occurring via telephone and 4% via a dedicated telehealth platform.

For LGS patients, the mean follow-up frequency is 8 months, while for DEEs patients it is 9 months, with no use of dedicated telehealth platforms reported.

The collected data allowed for the reconstruction of a comparative Patient Journey between DS and DEEs/LGS patients (Figure 4), structured into four key phases: pre-diagnosis, diagnosis, treatment initiation, and long-term management. This visual representation provides a concise overview of the complex steps patients and their families must navigate.

Based on physician and caregiver reports, the main differences between the two patient journeys include:

Pre-diagnosis:

Later symptom onset for DEEs/LGS (DS: within the first year of life; DEEs/LGS: within the first few years of life).

The survey confirms what emerged regarding the communication of the diagnosis, which was made by the child neuropsychiatrist in the absence of the psychologist in 75% of the cases. However, the perspective differs regarding the services provided post-diagnosis, where the majority of caregivers (53%) state that, in the case of DEEs/LGS, they did not receive any type of service, while a significant portion (24%) received care programs aimed at patients (Figure 5).

Very limited is also reported home care, where in 70% of cases the structures did not implement any resources or support services for this type of management, while a smaller proportion reported having access to rehabilitation services. On the other hand, communication regarding compensations and exemptions to which the patient could access was timely, and this was also the case for patients with DS. Up until the time of the interview, most caregivers stated that they had changed their referring doctor a mean of 3 times, mainly due to organizational changes within the facility, but also out of the desire to be properly followed and to explore new paths and therapeutic approaches; in total, the reference center changed for 53% of patients with a mean of 2.5 facilities, mainly to obtain a second opinion or for reasons similar to those mentioned for changing the specialist. The patients of the interviewed caregivers are currently followed mainly by individual specialists, in 53% of cases by a neurologist, in 41% of cases by a child neuropsychiatrist, and a small proportion by a general practitioner (6%). Multidisciplinary teams are reported only in 12% of cases.